Gene Detail

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Variant	Impact	Protein Effect	Variant Description
A17S	missense	no effect - predicted	CHEK2 A17S does not lie within any known functional domains of the Chek2 protein (UniProt.org). A17S results in levels of Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture (PMID: 34903604), and therefore, is predicted to have no effect on Chek2 protein function.
A230P	missense	loss of function - predicted	CHEK2 A230P lies within the protein kinase domain of the Chek2 protein (UniProt.org). A230P results in reduced phosphorylation of Chek2 and Kap1 upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
A237T	missense	loss of function - predicted	CHEK2 A237T lies within the protein kinase domain of the Chek2 protein (UniProt.org). A237T leads to a loss of growth inhibition in response to DNA damage (PMID: 33606978), and therefore, is predicted to lead to a loss of Chek2 protein function.
A247D	missense	loss of function	CHEK2 A247D lies within the protein kinase domain of the Chek2 protein (UniProt.org). A247D confers a loss of function to the Chek2 protein as demonstrated by decreased Chek2 protein expression and instability compared to wild-type Chek2 (PMID: 11719428) and decreased Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604).
A247T	missense	unknown	CHEK2 A247T lies within the protein kinase domain of the Chek2 protein (UniProt.org). A247T has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
A334T	missense	no effect - predicted	CHEK2 A334T lies within the protein kinase domain of the Chek2 protein (UniProt.org). A334T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
A392P	missense	loss of function - predicted	CHEK2 A392P lies within the protein kinase domain of the Chek2 protein (UniProt.org). A392P results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
A392S	missense	loss of function - predicted	CHEK2 A392S lies within the protein kinase domain of the Chek2 protein (UniProt.org). A392S results in moderately decreased autophosphorylation of Chek2 in cell culture (PMID: 28743916), and therefore, is predicted to lead to a loss of Check2 protein function.
A392V	missense	loss of function	CHEK2 A392V lies within the protein kinase domain of the Chek2 protein (UniProt.org). A392V results in decreased autophosphorylation of Chek2 (PMID: 28743916), leads to decreased Chek2 protein stability, and results in decreased Kap1 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604).
A480T	missense	unknown	CHEK2 A480T lies within the protein kinase domain of the Chek2 protein (UniProt.org). A480T results in intermediate levels of Kap1 and Chek2 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
A541G	missense	unknown	CHEK2 A541G does not lie within any known functional domains of the Chek2 protein (UniProt.org). A541G has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
amp	none	no effect	CHEK2 amplification indicates an increased number of copies of the CHEK2 gene. However, the mechanism causing the increase is unspecified.
C108R	missense	loss of function - predicted	CHEK2 C108R does not lie within any known functional domains of the Chek2 protein (UniProt.org). C108R results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
C243R	missense	no effect	CHEK2 C243R lies within the protein kinase domain of the Chek2 protein (UniProt.org). C243R results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and leads to levels of Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture (PMID: 34903604).
C284Y	missense	loss of function	CHEK2 C284Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). C284Y results in decreased Chek2 protein expression and phosphorylation in cultured cells and leads to a loss of growth inhibition in response to DNA damage (PMID: 33606978).
C385R	missense	loss of function - predicted	CHEK2 C385R lies within the protein kinase domain of the Chek2 protein (UniProt.org). C385R results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
C420T	missense	loss of function - predicted	CHEK2 C420T lies within the protein kinase domain of the Chek2 protein (UniProt.org). C420T results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
D134H	missense	no effect - predicted	CHEK2 D134H lies within the FHA domain of the Chek2 protein (UniProt.org). D134H results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D134Y	missense	unknown	CHEK2 D134Y lies within the FHA domain of the Chek2 protein (UniProt.org). D134Y has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
D162G	missense	loss of function - predicted	CHEK2 D162G lies within the FHA domain of the Chek2 protein (UniProt.org). D162G results in decreased cell proliferation in a yeast assay (PMID: 30851065), and decreased Kap1 phosphorylation and Chek2 protein stability in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
D203G	missense	unknown	CHEK2 D203G does not lie within any known functional domains of the Chek2 protein (UniProt.org). D203G results in intermediate levels of Kap1 and Chek2 phosphorylation upon ionizing radiation and reduced protein stability (PMID: 34903604), but leads to a splicing pattern similar to wild-type Chek2 protein in culture (PMID: 28608266), and therefore, its effect on Chek2 protein function is unknown.
D207V	missense	no effect - predicted	CHEK2 D207V does not lie within any known functional domains of the Chek2 protein (UniProt.org). D207V results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D265_H282del	deletion	loss of function	CHEK2 D265_H282del results in the deletion of 18 amino acids within the protein kinase domain of the Chek2 protein from amino acids 265 to 282 (UniProt.org). D265_H282del results in a loss of Kap1 phosphorylation at serine (S)-473 as compared to wild-type Chek2 in in vitro assays and in cell culture (PMID: 31050813).
D293fs	frameshift	loss of function - predicted	CHEK2 D293fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 293 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). D293fs has not been characterized, however, due to the effects of other truncation mutations downstream of D293 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
D311N	missense	no effect - predicted	CHEK2 D311N lies within the protein kinase domain of the Chek2 protein (UniProt.org). D311N results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D347A	missense	loss of function	CHEK2 D347A lies within the protein kinase domain of the Chek2 protein (UniProt.org). D347A results in the loss of Chk2 kinase activity as demonstrated by cell based assays (PMID: 9836640, PMID: 11298456), and results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604).
D347N	missense	loss of function	CHEK2 D347N lies within the protein kinase domain of the Chek2 protein (UniProt.org). D347N results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and leads to reduced Kap1 and Chek2 phosphorylation upon ionizing radiation in culture (PMID: 34903604).
D409N	missense	loss of function	CHEK2 D409N lies within the protein kinase domain of the Chek2 protein (UniProt.org). D409N results in reduced Chek2 protein stability and decreased Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604).
D438G	missense	no effect - predicted	CHEK2 D438G lies within the protein kinase domain of the Chek2 protein (UniProt.org). D438G results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D438Y	missense	unknown	CHEK2 D438Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). D438Y results in decreased Chek2 kinase activity in an in vitro kinase assay (PMID: 17721994), but results in intermediate levels of Kap1 and Chek2 phosphorylation upon ionizing radiation and reduced protein stability in cell culture (PMID: 34903604), and therefore, its effect on Chek2 protein function is unknown.
D490E	missense	no effect - predicted	CHEK2 D490E does not lie within any known functional domains of the Chek2 protein (UniProt.org). D490E results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D497N	missense	no effect - predicted	CHEK2 D497N does not lie within any known functional domains of the Chek2 protein (UniProt.org). D497N results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
D82_E86del	deletion	loss of function - predicted	CHEK2 D82_E86del results in the deletion of five amino acids in the Chek2 protein from amino acid 82 to 86 (UniProt.org). D82_E86del (reported as P75_E79del) results in decreased Chek2 kinase activity in an in vitro assay (PMID: 17721994), and therefore, is predicted to lead to a loss of Chek2 protein function.
dec exp	none	no effect	CHEK2 dec exp indicates decreased expression of the Chek2 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
del	deletion	loss of function	CHEK2 del indicates a deletion of the CHEK2 gene.
E107_K197del	deletion	loss of function - predicted	CHEK2 E107_K197del results in the deletion of ninety one amino acids in the Chek2 protein from amino acid 107 to 197 (UniProt.org). E107_K197del results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
E122Dfs*8	frameshift	loss of function - predicted	CHEK2 E122Dfs8 indicates a shift in the reading frame starting at amino acid 122 and terminating 8 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). E122Dfs8 has not been characterized, however, due to the effects of other truncation mutations downstream of E122 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
E149Ifs*6	frameshift	loss of function - predicted	CHEK2 E149Ifs6 indicates a shift in the reading frame starting at amino acid 149 and terminating 6 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). E149Ifs6 has not been characterized, however, due to the effects of other truncation mutations downstream of E149 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
E161del	deletion	loss of function	CHEK2 E161del results in the deletion of an amino acid in the FHA domain of the Chek2 protein at amino acid 161 (UniProt.org). E161del confers a loss of function to the Chek2 protein as demonstrated by reduced tyrosine phosphorylation in response to DNA damage in culture (PMID: 16982735).
E239K	missense	loss of function	CHEK2 E239K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E239K confers a loss of function on Chek2 as indicated by reduced Chek2-mediated DNA damage repair in yeast (PMID: 22419737), and decreased Chek2 protein expression and phosphorylation in cultured cells (PMID: 33606978).
E239Q	missense	no effect - predicted	CHEK2 E239Q lies within the protein kinase domain of the Chek2 protein (UniProt.org). E239Q results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E263Q	missense	no effect - predicted	CHEK2 E263Q lies within the protein kinase domain of the Chek2 protein (UniProt.org). E263Q results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E273K	missense	loss of function - predicted	CHEK2 E273K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E273K results in Chek2 autophosphorylation upon ionizing radiation similar to wild-type Chek2, but leads to reduced Kap1 phosphorylation (PMID: 34903604), and therefore, is predicted to lead to a loss of Kap1 protein function.
E275*	nonsense	loss of function - predicted	CHEK2 E275* results in a premature truncation within the protein kinase domain of the Chek2 protein at amino acid 275 of 543 (UniProt.org). E275* has not been characterized, however, due to the effects of other truncation mutations downstream of E275 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
E275K	missense	unknown	CHEK2 E275K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E275K has been identified in the scientific literature (PMID: 38773265), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
E305G	missense	unknown	CHEK2 E305G lies within the protein kinase domain of the Chek2 protein (UniProt.org). E305G has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
E321*	nonsense	loss of function - predicted	CHEK2 E321* results in a premature truncation within the protein kinase domain of the Chek2 protein at amino acid 321 of 543 (UniProt.org). E321* has not been characterized, however, due to the effects of other truncation mutations downstream of E321 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
E321K	missense	loss of function	CHEK2 E321K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E321K confers a loss of function to the Chek2 protein as demonstrated by a loss of kinase activity (PMID: 16835864).
E351D	missense	unknown	CHEK2 E351D lies within the protein kinase domain of the Chek2 protein (UniProt.org). E351D results in Chek2 phosphorylation similar to wild-type Chek2, but leads to reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, its effect on Chek2 protein function is unknown.
E351K	missense	loss of function	CHEK2 E351K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E351K results in decreased Chek2 protein expression and phosphorylation in cultured cells and leads to a loss of growth inhibition in response to DNA damage (PMID: 33606978).
E377G	missense	no effect - predicted	CHEK2 E377G lies within the protein kinase domain of the Chek2 protein (UniProt.org). E377G results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E394K	missense	loss of function	CHEK2 E394K lies within the protein kinase domain of the Chek2 protein (UniProt.org). E394K results in a loss of Kap1 phosphorylation at serine (S)-473 as compared to wild-type Chek2 in culture and in vitro assays (PMID: 31050813).
E454V	missense	unknown	CHEK2 E454V lies within the protein kinase domain of the Chek2 protein (UniProt.org). E454V has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
E501K	missense	no effect - predicted	CHEK2 E501K does not lie within any known functional domains of the Chek2 protein (UniProt.org). E501K results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E504Q	missense	no effect - predicted	CHEK2 E504Q does not lie within any known functional domains of the Chek2 protein (UniProt.org). E504Q results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E528K	missense	no effect - predicted	CHEK2 E528K does not lie within any known functional domains of the Chek2 protein (UniProt.org). E528K results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E531Q	missense	no effect - predicted	CHEK2 E531Q does not lie within any known functional domains of the Chek2 protein (UniProt.org). E531Q results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
E64K	missense	loss of function	CHEK2 E64K does not lie within any known functional domains of the Chek2 protein (UniProt.org). E64K confers a loss of function to Chek2 protein as indicated by a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), decreased Kap1 phosphorylation in response to radiation (PMID: 34903604), and reduced Chek2 expression and phosphorylation in culture (PMID: 33606978).
E87*	nonsense	loss of function - predicted	CHEK2 E87* results in a premature truncation of the Chek2 protein at amino acid 87 of 543 (UniProt.org). E87* has not been characterized, however, due to the effects of other truncations downstream of E87 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
F103L	missense	no effect - predicted	CHEK2 F103L does not lie within any known functional domains of the Chek2 protein (UniProt.org). F103L results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
F125S	missense	loss of function - predicted	CHEK2 F125S lies within the FHA domain of the Chek2 protein (UniProt.org). F125S results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
F169L	missense	loss of function - predicted	CHEK2 F169L lies within the FHA domain of the Chek2 protein (UniProt.org). F169L results in reduced Kap1 phosphorylation at serine (S)-473 upon ionizing radiation in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
F169Lfs*2	frameshift	loss of function - predicted	CHEK2 F169Lfs2 indicates a shift in the reading frame starting at amino acid 169 and terminating 2 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). F169Lfs2 results in reduced Kap1 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
F202fs	frameshift	loss of function - predicted	CHEK2 F202fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 202 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). F202fs has not been characterized, however, due to the effects of other truncation mutations downstream of F202 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
F292fs	frameshift	loss of function - predicted	CHEK2 F292fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 292 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). F292fs has not been characterized, however, due to the effects of other truncation mutations downstream of F292 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
F475I	missense	no effect - predicted	CHEK2 F475I lies within the protein kinase domain of the Chek2 protein (UniProt.org). F475I results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
F475Lfs*7	frameshift	loss of function - predicted	CHEK2 F475Lfs7 indicates a shift in the reading frame starting at amino acid 475 and terminating 7 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). F475Lfs7 is predicted to confer a loss of function to the Chek2 protein as demonstrated by a loss of kinase activity in an in vitro assay (PMID: 11053450).
G102V	missense	unknown	CHEK2 G102V does not lie within any known functional domains of the Chek2 protein (UniProt.org). G102V has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
G116A	missense	unknown	CHEK2 G116A lies within the FHA domain of the Chek2 protein (UniProt.org). G116A has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, May 2024).
G14Afs*47	frameshift	loss of function - predicted	CHEK2 G14Afs47 indicates a shift in the reading frame starting at amino acid 14 and terminating 47 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). Due to loss of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), G14Afs47 is predicted to lead to a loss of Chek2 protein function.
G151C	missense	no effect - predicted	CHEK2 G151C lies within the FHA domain of the Chek2 protein (UniProt.org). G151C results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
G167R	missense	loss of function	CHEK2 G167R lies within the FHA domain of the Chek2 protein (UniProt.org). G167R results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737) and reduced Kap1 phosphorylation and Chek2 protein stability compared to wild-type Chek2 in culture (PMID: 34903604).
G229D	missense	unknown	CHEK2 G229D lies within the protein kinase domain of the Chek2 protein (UniProt.org). G229D has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, May 2024).
G229S	missense	loss of function - predicted	CHEK2 G229S lies within the protein kinase domain of the Chek2 protein (UniProt.org). G229S results in reduced phosphorylation of Chek2 and Kap1 upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
G232R	missense	unknown	CHEK2 G232R lies within the protein kinase domain of the Chek2 protein (UniProt.org). G232R has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
G306A	missense	loss of function	CHEK2 G306A lies within the protein kinase domain of the Chek2 protein (UniProt.org). G306A results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and loss of Kap1 phosphorylation at serine (S)-473 as compared to wild-type Chek2 in culture and in vitro assays (PMID: 31050813).
G306E	missense	loss of function - predicted	CHEK2 G306E lies within the protein kinase domain of the Chek2 protein (UniProt.org). G306E results in reduced phosphorylation of Chek2 and Kap1 upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
G306W	missense	unknown	CHEK2 G306W lies within the protein kinase domain of the Chek2 protein (UniProt.org). G306W has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
G342S	missense	no effect - predicted	CHEK2 G342S lies within the protein kinase domain of the Chek2 protein (UniProt.org). G342S results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
G370E	missense	loss of function - predicted	CHEK2 G370E lies within the protein kinase domain of the Chek2 protein (UniProt.org). G370E results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
G386R	missense	loss of function - predicted	CHEK2 G386R lies within the protein kinase domain of the Chek2 protein (UniProt.org). G386R results in Chek2 protein stability similar to wild-type Chek2, but results in reduced Kap1 phosphorylation and Chek2 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss Chek2 protein function.
G414E	missense	loss of function - predicted	CHEK2 G414E lies within the protein kinase domain of the Chek2 protein (UniProt.org). G414E results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
H143R	missense	loss of function - predicted	CHEK2 H143R lies within the FHA domain of the Chek2 protein (UniProt.org). H143R results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
H143Y	missense	loss of function - predicted	CHEK2 H143Y lies within the FHA domain of the Chek2 protein (UniProt.org). H143Y results in decreased Chek2 protein stability in culture (PMID: 17721994), and therefore, is predicted to lead to a loss of Chek2 protein function.
H282Y	missense	unknown	CHEK2 H282Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). H282Y has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, May 2024).
H339Y	missense	unknown	CHEK2 H339Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). H339Y has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
H371Y	missense	unknown	CHEK2 H371Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). H371Y results in reduced basal tyrosine phosphorylation and reduced tyrosine phosphorylation in response to DNA damage (PMID: 21618645), but results in levels of Kap1 phosphorylation at serine (S)-473 upon ionizing radiation similar to wild-type Chek2 in cell culture (PMID: 34903604), and therefore, its effect on Chek2 protein function is unknown.
H483R	missense	loss of function - predicted	CHEK2 H483R lies within the protein kinase domain of the Chek2 protein (UniProt.org). H483R results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
H54Pfs*6	frameshift	loss of function - predicted	CHEK2 H54Pfs6 indicates a shift in the reading frame starting at amino acid 54 and terminating 6 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). H54Pfs6 has not been characterized, however, due to the effects of other truncation mutations downstream of H54 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
I157S	missense	no effect - predicted	CHEK2 I157S lies within the FHA domain of the Chek2 protein (UniProt.org). I157S results in levels of Kap1 phosphorylation at serine (S)-473 upon ionizing radiation similar to wild-type Chek2 in cell culture (PMID: 34903604), and therefore, is predicted to have no effect on Chek2 protein function.
I157T	missense	loss of function - predicted	CHEK2 I157T lies within the FHA domain of the Chek2 protein (UniProt.org). I157T displays kinase activity similar to wild-type Chek2 in an in vitro assay (PMID: 11053450), but fails to form dimers required for activation (PMID: 19782031) and has impaired binding to several proteins, including BRCA1 in cultured cells (PMID: 12049740), and therefore, is predicted to lead to a loss of Chek2 protein function.
I160M	missense	loss of function - predicted	CHEK2 I160M lies within the FHA domain of the Chek2 protein (UniProt.org). I160M results in decreased Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
I160R	missense	loss of function - predicted	CHEK2 I160R lies within the FHA domain of the Chek2 protein (UniProt.org). I160R results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
I160T	missense	loss of function - predicted	CHEK2 I160T lies within the FHA domain of the Chek2 protein (UniProt.org). I160T results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
I189V	missense	loss of function - predicted	CHEK2 I189V does not lie within any known functional domains of the Chek2 protein (UniProt.org). I189V results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
I221M	missense	no effect - predicted	CHEK2 I221M lies within the protein kinase domain of the Chek2 protein (UniProt.org). I221M results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
I221V	missense	no effect - predicted	CHEK2 I221V lies within the protein kinase domain of the Chek2 protein (UniProt.org). I221V results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
I251F	missense	unknown	CHEK2 I251F lies within the protein kinase domain of the Chek2 protein (UniProt.org). I251F results in intermediate levels of Chek2 phosphorylation and decreased Kap1 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
I251M	missense	unknown	CHEK2 I251M lies within the protein kinase domain of the Chek2 protein (UniProt.org). I251M has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
I276S	missense	unknown	CHEK2 I276S lies within the protein kinase domain of the Chek2 protein (UniProt.org). I276S has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
I364T	missense	unknown	CHEK2 I364T lies within the protein kinase domain of the Chek2 protein (UniProt.org). I364T results in a loss of Kap1 phosphorylation at serine (S)-473 (PMID: 31050813) and reduced Cdc25-phosphorylation and Chek2 autophosphorylation (PMID: 18725978) in in vitro assays, but similar levels of Kap1 phosphorylation in a cell culture system that preserves post-translational modifications of Chek2 (PMID: 31050813), similar ability to dimerize with wild-type Chek2 in an in vitro assay (PMID: 18725978), and intermediate cell proliferation in a yeast assay compared to wild-type Chek2 (PMID: 30851065), and therefore, its effect on Chek2 protein function is unknown.
I448S	missense	unknown	CHEK2 I448S lies within the protein kinase domain of the Chek2 protein (UniProt.org). I448S results in intermediate levels of Kap1 phosphorylation, and Chek2 phosphorylation similar to wild-type Chek2 upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
inact mut	unknown	loss of function	CHEK2 inact mut indicates that this variant results in a loss of function of the Chek2 protein. However, the specific amino acid change has not been identified.
K135Nfs*26	frameshift	loss of function - predicted	CHEK2 K135Nfs26 indicates a shift in the reading frame starting at amino acid 135 and terminating 26 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). K135Nfs26 results in reduced Kap1 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
K135T	missense	unknown	CHEK2 K135T lies within the FHA domain of the Chek2 protein (UniProt.org). K135T has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
K141T	missense	unknown	CHEK2 K141T lies within the FHA domain of the Chek2 protein (UniProt.org). K141T results in intermediate levels of Kap1 and Chek2 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
K224E	missense	loss of function - predicted	CHEK2 K224E lies within the protein kinase domain of the Chek2 protein (UniProt.org). K224E results in a loss of kinase activity in an in vitro assay (PMID: 22114986), and therefore, is predicted to lead to a loss of Chek2 protein function.
K244R	missense	no effect - predicted	CHEK2 K244R lies within the protein kinase domain of the Chek2 protein (UniProt.org). K244R results in kinase activity similar to wild-type Chek2 in an in vitro assay (PMID: 22114986), and therefore, is predicted to have no effect on Chek2 protein function.
K249N	missense	unknown	CHEK2 K249N lies within the protein kinase domain of the Chek2 protein (UniProt.org). K249N has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Jul 2024).
K249R	missense	loss of function - predicted	CHEK2 K249R lies within the protein kinase domain of the Chek2 protein (UniProt.org). K249R results in reduced phosphorylation of Chek2 and Kap1 upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
K253*	nonsense	loss of function - predicted	CHEK2 K253* results in a premature truncation of the Chek2 protein at amino acid 253 of 543 (UniProt.org). K253* results in decreased Kap1 phosphorylation at (S)-473 upon ionizing radiation in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
K279T	missense	unknown	CHEK2 K279T lies within the protein kinase domain of the Chek2 protein (UniProt.org). K279T has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
K287fs	frameshift	loss of function - predicted	CHEK2 K287fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 287 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). K287fs has not been characterized, however, due to the effects of other truncation mutations downstream of K287 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
K373E	missense	loss of function	CHEK2 K373E lies within the protein kinase domain of the Chek2 protein (UniProt.org). K373E results in decreased Chek2 kinase activity and autophosphorylation, and fails to inhibit cell proliferation or promote survival following radiation in cell culture (PMID: 27716909).
K373R	missense	no effect - predicted	CHEK2 K373R lies within the protein kinase domain of the Chek2 protein (UniProt.org). K373R results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
K437E	missense	no effect	CHEK2 K437E lies within the protein kinase domain of the Chek2 protein (UniProt.org). K437E results in similar Kap1 phosphorylation at serine (S)-473 as compared to wild-type Chek2 in in vitro assays and in cell culture (PMID: 31050813).
L174F	missense	no effect - predicted	CHEK2 L174F lies within the FHA domain of the Chek2 protein (UniProt.org). L174F results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
L174V	missense	loss of function - predicted	CHEK2 L174V lies within the FHA domain of the Chek2 protein (UniProt.org). L174V phosphorylates Kap1 at serine (S)-473 to similar levels as wild-type Chek2 in in vitro assays, but results in a loss of Kap1 phosphorylation in a cell culture system that preserves posttranslational modifications of Chek2 (PMID: 31050813), and therefore, is predicted to lead to a loss of Chek2 protein function.
L183F	missense	loss of function - predicted	CHEK2 L183F does not lie within any known functional domains of the Chek2 protein (UniProt.org). L183F results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
L183S	missense	loss of function - predicted	CHEK2 L183S does not lie within any known functional domains of the Chek2 protein (UniProt.org). L183S results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
L216*	nonsense	loss of function - predicted	CHEK2 L216* results in a premature truncation of the Chek2 protein at amino acid 216 of 543 (UniProt.org). L216* has not been characterized, however, due to the effects of other truncations downstream of L216 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
L226F	missense	unknown	CHEK2 L226F lies within the protein kinase domain of the Chek2 protein (UniProt.org). L226F has been identified in sequencing studies (PMID: 27442865), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
L236P	missense	loss of function - predicted	CHEK2 L236P lies within the protein kinase domain of the Chek2 protein (UniProt.org). L236P results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
L309P	missense	loss of function - predicted	CHEK2 L309P lies within the protein kinase domain of the Chek2 protein (UniProt.org). L309P results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
L326P	missense	loss of function - predicted	CHEK2 L326P lies within the protein kinase domain of the Chek2 protein (UniProt.org). L326P results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
L338F	missense	no effect - predicted	CHEK2 L338F lies within the protein kinase domain of the Chek2 protein (UniProt.org). L338F results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
L338R	missense	unknown	CHEK2 L338R lies within the protein kinase domain of the Chek2 protein (UniProt.org). L338R has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
L354V	missense	unknown	CHEK2 L354V lies within the protein kinase domain of the Chek2 protein (UniProt.org). L354V has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
L355P	missense	unknown	CHEK2 L355P lies within the protein kinase domain of the Chek2 protein (UniProt.org). L355P has been identified in sequencing studies (PMID: 18186519, PMID: 17145815), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
L396V	missense	unknown	CHEK2 L396V lies within the protein kinase domain of the Chek2 protein (UniProt.org). L396V has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
L512V	missense	no effect - predicted	CHEK2 L512V does not lie within any known functional domains of the Chek2 protein (UniProt.org). L512V results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
L543S	missense	unknown	CHEK2 L543S does not lie within any known functional domains of the Chek2 protein (UniProt.org). L543S has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Nov 2024).
loss	unknown	loss of function	CHEK2 loss indicates loss of the CHEK2 gene, mRNA, and protein.
M222V	missense	no effect - predicted	CHEK2 M222V lies within the protein kinase domain of the Chek2 protein (UniProt.org). M222V results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
M304T	missense	loss of function - predicted	CHEK2 M304T lies within the protein kinase domain of the Chek2 protein (UniProt.org). M304T results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
M381*	nonsense	loss of function - predicted	CHEK2 M381* results in a premature truncation within the protein kinase domain of the Chek2 protein at amino acid 381 of 543 (UniProt.org). M381* has not been characterized, however, due to the effects of other truncation mutations downstream of M381 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
M381V	missense	no effect - predicted	CHEK2 M381V lies within the protein kinase domain of the Chek2 protein (UniProt.org). M381V results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
mutant	unknown	unknown	CHEK2 mutant indicates an unspecified mutation in the CHEK2 gene.
N166S	missense	loss of function - predicted	CHEK2 N166S lies within the FHA domain of the Chek2 protein (UniProt.org). N166S results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
N185fs	frameshift	loss of function - predicted	CHEK2 N185fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 185 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). N185fs has not been characterized, however, due to the effects of other truncation mutations downstream of N185 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
N185T	missense	unknown	CHEK2 N185T does not lie within any known functional domains of the Chek2 protein (UniProt.org). N185T has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
N186H	missense	no effect	CHEK2 N186H does not lie within any known functional domains of the Chek2 protein (UniProt.org). N186H results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and leads to Chek2 protein stability and levels of Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture (PMID: 34903604).
N281S	missense	no effect - predicted	CHEK2 N281S lies within the protein kinase domain of the Chek2 protein (UniProt.org). N281S results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
N290Ifs*15	frameshift	loss of function - predicted	CHEK2 N290Ifs15 indicates a shift in the reading frame starting at amino acid 290 and terminating 15 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). N290Ifs15 has not been characterized, however, due to the effects of other truncation mutations downstream of N290 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
N352D	missense	loss of function - predicted	CHEK2 N352D lies within the protein kinase domain of the Chek2 protein (UniProt.org). N352D results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
N405K	missense	no effect - predicted	CHEK2 N405K lies within the protein kinase domain of the Chek2 protein (UniProt.org). N405K results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
N446D	missense	no effect	CHEK2 N446D lies within the protein kinase domain of the Chek2 protein (UniProt.org). N446D results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065) and results in levels of Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture (PMID: 34903604).
over exp	none	no effect	CHEK2 over exp indicates an over expression of the Chek2 protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
P182H	missense	unknown	CHEK2 P182H does not lie within any known functional domains of the Chek2 protein (UniProt.org). P182H has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
P182L	missense	unknown	CHEK2 P182L does not lie within any known functional domains of the Chek2 protein (UniProt.org). P182L has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
P182T	missense	no effect - predicted	CHEK2 P182T does not lie within any known functional domains of the Chek2 protein (UniProt.org). P182T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
P21T	missense	no effect - predicted	CHEK2 P21T does not lie within any known functional domains of the Chek2 protein (UniProt.org). P21T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
P425L	missense	unknown	CHEK2 P425L lies within the protein kinase domain of the Chek2 protein (UniProt.org). P425L results in a loss of Kap1 phosphorylation at serine (S)-473 in culture, but demonstrates conflicting effects on Kap1 phosphorylation in in vitro assays (PMID: 31050813), and therefore, its effect on Chek2 protein function is unknown.
P426H	missense	unknown	CHEK2 P426H lies within the protein kinase domain of the Chek2 protein (UniProt.org). P426H has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, May 2024).
P426R	missense	loss of function - predicted	CHEK2 P426R lies within the protein kinase domain of the Chek2 protein (UniProt.org). P426R results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
P484L	missense	no effect - predicted	CHEK2 P484L lies within the protein kinase domain of the Chek2 protein (UniProt.org). P484L results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
P484T	missense	no effect - predicted	CHEK2 P484T lies within the protein kinase domain of the Chek2 protein (UniProt.org). P484T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
P509S	missense	unknown	CHEK2 P509S does not lie within any known functional domains of the Chek2 protein (UniProt.org). P509S results in levels of Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture (PMID: 31050813, PMID: 34903604) and in vitro assays (PMID: 31050813), but demonstrates intermediate cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, its effect on Chek2 protein function is unknown.
P536L	missense	unknown	CHEK2 P536L does not lie within any known functional domains of the Chek2 protein (UniProt.org). P536L has been identified in the scientific literature (PMID: 23243591, PMID: 25980754), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
P80H	missense	no effect - predicted	CHEK2 P80H does not lie within any known functional domains of the Chek2 protein (UniProt.org). P80H results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
P85L	missense	unknown	CHEK2 P85L does not lie within any known functional domains of the Chek2 protein (UniProt.org). P85L results in decreased Chek2 kinase activity in an in vitro kinase assay (PMID: 17721994) but DNA repair activity similar to wild-type Chek2 in a yeast assay (PMID: 22419737) and complements Rad53 loss similar to wild-type in a yeast assay (PMID: 15649950), and therefore, its effect on Chek2 protein function is unknown.
P85R	missense	loss of function - predicted	CHEK2 P85R does not lie within any known functional domains of the Chek2 protein (UniProt.org). P85R results in decreased kinase activity in an in vitro assay (PMID: 22114986), and therefore, is predicted to lead to a loss of Chek2 protein function.
P90S	missense	unknown	CHEK2 P90S does not lie within any known functional domains of the Chek2 protein (UniProt.org). P90S has been identified in sequencing studies (PMID: 26580448), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
Q10fs	frameshift	loss of function - predicted	CHEK2 Q10fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 10 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). Q10fs has not been characterized, however, due to the effects of other truncation mutations downstream of Q10 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
Q209*	nonsense	loss of function	CHEK2 Q209* results in a premature truncation of the Chek2 protein at amino acid 209 of 543 (UniProt.org). Q209* results in decreased Chek2 protein expression and phosphorylation in cultured cells and leads to a loss of growth inhibition in response to DNA damage (PMID: 33606978).
Q27*	nonsense	loss of function - predicted	CHEK2 Q27* results in a premature truncation of the Chek2 protein at amino acid 27 of 543 (UniProt.org). Q27* has not been characterized, however, due to the effects of other truncations downstream of Q27 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
Q34Vfs*42	frameshift	loss of function - predicted	CHEK2 Q34Vfs42 indicates a shift in the reading frame starting at amino acid 34 and terminating 42 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). Q34Vfs42 has not been characterized, however, due to the effects of other truncation mutations downstream of Q34 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
Q487R	missense	unknown	CHEK2 Q487R does not lie within any known functional domains of the Chek2 protein (UniProt.org). Q487R has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R117A	missense	loss of function	CHEK2 R117A lies within the FHA domain of the Chek2 protein (UniProt.org). R117A confers a loss of function to the Chek 2 protein as demonstrated by failure to bind several proteins, including BRCA1 in pull-down assays (PMID: 12049740).
R117G	missense	loss of function	CHEK2 R117G lies within the FHA domain of the Chek2 protein (UniProt.org). R117G confers a loss of function to the Chek2 protein as demonstrated by reduced kinase activity (PMID: 16835864), and results in decreased Kap1 phosphorylation upon ionizing radiation in cell culture (PMID: 34903604).
R137Q	missense	no effect - predicted	CHEK2 R137Q lies within the FHA domain of the Chek2 protein (UniProt.org). R137Q demonstrates kinase activity similar to wild-type Chek2 in cell culture (PMID: 17721994, PMID: 22114986), and therefore, is predicted to have no effect on Chek2 protein function.
R145Q	missense	no effect - predicted	CHEK2 R145Q lies within the FHA domain of the Chek2 protein (UniProt.org). R145Q results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
R145W	missense	loss of function	CHEK2 R145W lies in the FHA domain of the Chek2 protein (UniProt.org). R145W results in decreased Kap1 phosphorylation upon ionizing radiation, decreased Chek2 protein stability compared to wild-type Chek2 (PMID: 34903604), reduced Chek2 kinase activity and impaired activation by gamma irradiation in cell-based assays (PMID: 11053450), and fails to bind several proteins, including BRCA1 in pull-down assays (PMID: 12049740).
R148G	missense	loss of function - predicted	CHEK2 R148G lies within the FHA domain of the Chek2 protein (UniProt.org). R148G results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
R148T	missense	no effect - predicted	CHEK2 R148T lies within the FHA domain of the Chek2 protein (UniProt.org). R148T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
R180C	missense	unknown	CHEK2 R180C does not lie within any known functional domains of the Chek2 protein (UniProt.org). The functional effect of R180C is conflicting, as it results in cell proliferation similar to wild-type Chek2 in a yeast assay in one study (PMID: 30851065), however, results in intermediate cell proliferation relative to wild-type Chek2 in another study (PMID: 22419737), and similar Kap1 phosphorylation at serine (S)-473 in cell culture and in vitro assays (PMID: 31050813, PMID: 34903604), and therefore, its effect on Chek2 protein function is unknown.
R180H	missense	loss of function - predicted	CHEK2 R180H does not lie within any known functional domains of the Chek2 protein (UniProt.org). R180H results in decreased kinase activity in an in vitro assay (PMID: 22114986), and therefore, is predicted to lead to a loss of Chek2 protein function.
R181C	missense	unknown	CHEK2 R181C does not lie within any known functional domains of the Chek2 protein (UniProt.org). R181C results in kinase activity similar to wild-type Chek2 in a kinase assay and in cultured cells (PMID: 31050813), but decreased Chek2 kinase activity in an in vitro assay in another study (PMID: 16835864), and decreased DNA damage response in yeast (PMID: 22419737), and therefore, its effect on Chek2 protein function is unknown.
R181H	missense	no effect	CHEK2 R181H does not lie within any known functional domains of the Chek2 protein (PMID: 31050813). R181H results in Kap1 phosphorylation at serine (S)-473 similar to wild-type Chek2 in cell culture and in vitro assays (PMID: 31050813, PMID: 34903604), and similar cell proliferation in a yeast assay (PMID: 30851065).
R318C	missense	no effect - predicted	CHEK2 R318C lies within the protein kinase domain of the Chek2 protein (UniProt.org). R318C results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
R318H	missense	loss of function - predicted	CHEK2 R318H lies within the protein kinase domain of the Chek2 protein (UniProt.org). R318H results in decreased Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
R346C	missense	unknown	CHEK2 R346C lies within the protein kinase domain of the Chek2 protein (UniProt.org). R346C has been identified in the scientific literature (PMID: 27595995), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R346G	missense	unknown	CHEK2 R346G lies within the protein kinase domain of the Chek2 protein (UniProt.org). R346G has been identified in the scientific literature (PMID: 26981779), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R346H	missense	unknown	CHEK2 R346H lies within the protein kinase domain of the Chek2 protein (UniProt.org). The functional effect of R346H is conflicting, as it results in a loss of Chek2 phosphorylation (PMID: 34903604) and loss of Kap1 phosphorylation at serine (S)-473 in cell culture and an in vitro assay (PMID: 31050813, PMID: 34903604) however, in another in vitro assay, R346H demonstrates similar Kap1 phosphorylation levels as wild-type Chek2 (PMID: 31050813), and therefore, its effect on Chek2 protein function is unknown.
R346S	missense	unknown	CHEK2 R346S lies within the protein kinase domain of the Chek2 protein (UniProt.org). R346S has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R382*	nonsense	loss of function - predicted	CHEK2 R382* results in a premature truncation of the Chek2 protein at amino acid 382 of 543 (UniProt.org). R382* has not been characterized, however, due to the effects of other truncation mutations downstream of R382 resulting in disruption of the protein kinase domain (PMID: 11053450), is predicted to lead to a loss of Chek2 protein function.
R3W	missense	unknown	CHEK2 R3W does not lie within any known functional domains of the Chek2 protein (UniProt.org). The functional effect of R3W is conflicting, as it results in cell proliferation similar to wild-type Chek2 in a yeast assay in one study (PMID: 30851065), however, results in intermediate cell proliferation relative to wild-type Chek2 in another study (PMID: 22419737), and similar Kap1 phosphorylation at serine (S)-473 in cell culture and in vitro assays (PMID: 31050813), and therefore, its effect on Chek2 protein function is unknown.
R406C	missense	no effect - predicted	CHEK2 R406C lies within the protein kinase domain of the Chek2 protein (UniProt.org). R406C results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
R406H	missense	unknown	CHEK2 R406H lies within the protein kinase domain of the Chek2 protein (UniProt.org). R406H results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and intermediate Kap1 phosphorylation levels at serine (S)-473 in culture, but demonstrates conflicting effects on Kap1 phosphorylation in in vitro assays (PMID: 31050813), and therefore, its effect on Chek2 protein function is unknown.
R406Vfs*8	frameshift	loss of function - predicted	CHEK2 R406Vfs8 indicates a shift in the reading frame starting at amino acid 406 and terminating 8 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). R406Vfs8 has not been characterized, however, due to the effects of other truncation mutations downstream of R406 resulting in disruption of the protein kinase domain (PMID: 11053450), is predicted to lead to a loss of Chek2 protein function.
R474C	missense	loss of function	CHEK2 R474C lies within the protein kinase domain of the Chek2 protein (UniProt.org). R474C confers a loss of function to Chek2 as demonstrated by decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), decreased protein expression, and decreased autophosphorylation upon irradiation in culture (PMID: 27900359).
R474H	missense	loss of function	CHEK2 R474H lies within the protein kinase domain of the Chek2 protein (UniProt.org). R474H results in decreased Chek2 protein stability in culture (PMID: 34903604), and results in a loss of Kap1 phosphorylation at serine (S)-473 compared to wild-type Chek2 in culture and in vitro assays (PMID: 31050813, PMID: 34903604).
R474L	missense	loss of function - predicted	CHEK2 R474L lies within the protein kinase domain of the Chek2 protein (UniProt.org). R474L results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
R519*	nonsense	unknown	CHEK2 R519* results in a premature truncation of the Chek2 protein at amino acid 519 of 543 (UniProt.org). R519* results in intermediate levels of Kap phosphorylation upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
R519G	missense	unknown	CHEK2 R519G does not lie within any known functional domains of the Chek2 protein (UniProt.org). R519G has been identified in the scientific literature (PMID: 24879340, PMID: 24413734), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R521Q	missense	unknown	CHEK2 R521Q does not lie within any known functional domains of the Chek2 protein (UniProt.org). R521Q results in impaired nuclear localization (PMID: 37449874), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
R521W	missense	unknown	CHEK2 R521W does not lie within any known functional domains of the Chek2 protein (UniProt.org). R521W results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), but results in intermediate levels of Kap1 and Chek2 phosphorylation upon ionizing radiation and reduced protein stability in cell culture (PMID: 34903604), and therefore, its effect on Chek2 protein function is unknown.
R523C	missense	no effect - predicted	CHEK2 R523C does not lie within any known functional domains of the Chek2 protein (UniProt.org). R523C results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
R523fs	frameshift	unknown	CHEK2 R523fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 523 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). R523fs has been identified in sequencing studies (PMID: 32183364), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, May 2024).
R95*	nonsense	loss of function - predicted	CHEK2 R95* results in a premature truncation of the Chek2 protein at amino acid 95 of 543 (UniProt.org). R95* has not been characterized, however, due to the effects of other truncation mutations downstream of R95 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
S140N	missense	loss of function - predicted	CHEK2 S140N lies within the FHA domain of the Chek2 protein (UniProt.org). S140N results in reduced phosphorylation of Chek2 and Kap1 upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
S24C	missense	unknown	CHEK2 S24C does not lie within any known functional domains of the Chek2 protein (UniProt.org). S24C has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
S357F	missense	loss of function - predicted	CHEK2 S357F lies within the protein kinase domain of the Chek2 protein (UniProt.org). S357F results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
S372F	missense	loss of function - predicted	CHEK2 S372F lies within the protein kinase domain of the Chek2 protein (UniProt.org). S372F results in decreased autophosphorylation of Chek2 in cell culture (PMID: 28743916), and therefore, is predicted to lead to a loss of Chek2 protein function.
S372Y	missense	loss of function - predicted	CHEK2 S372Y lies within the protein kinase domain of the Chek2 protein (UniProt.org). S372Y results in decreased autophosphorylation of Chek2 in cell culture (PMID: 28743916), and therefore, is predicted to lead to a loss of Check2 protein function.
S39F	missense	no effect - predicted	CHEK2 S39F does not lie within any known functional domains of the Chek2 protein (UniProt.org). S39F demonstrates kinase activity similar to wildtype Chek2 in cell culture (PMID: 22114986), and therefore, is predicted to have no effect on Chek2 protein function.
S412R	missense	loss of function - predicted	CHEK2 S412R lies within the protein kinase domain of the Chek2 protein (UniProt.org). S412R results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
S422Vfs*15	frameshift	loss of function - predicted	CHEK2 S422Vfs15 indicates a shift in the reading frame starting at amino acid 422 and terminating 15 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). S422Vfs15 results in decreased Kap1 phosphorylation at (S)-473 in cell culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
S428F	missense	loss of function - predicted	CHEK2 S428F lies within the protein kinase domain of the Chek2 protein (UniProt.org). S428F results in decreased Chek2 activity in yeast complementation assays (PMID: 15649950), and therefore, is predicted to lead to a loss of Chek2 protein function.
S49F	missense	unknown	CHEK2 S49F does not lie within any known functional domains of the Chek2 protein (UniProt.org). S49F has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
S505T	missense	no effect - predicted	CHEK2 S505T does not lie within any known functional domains of the Chek2 protein (UniProt.org). S505T results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
S57F	missense	no effect - predicted	CHEK2 S57F does not lie within any known functional domains of the Chek2 protein (UniProt.org). S57F results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
S5L	missense	no effect - predicted	CHEK2 S5L does not lie within any known functional domains of the Chek2 protein (UniProt.org). S5L results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
T168I	missense	unknown	CHEK2 T168I lies within the FHA domain of the Chek2 protein (UniProt.org). T168I results in a loss of Kap1 phosphorylation at serine (S)-473 in culture, but demonstrates conflicting effects on Kap1 phosphorylation in in vitro assays (PMID: 31050813), and therefore, its effect on Chek2 protein function is unknown.
T172A	missense	no effect - predicted	CHEK2 T172A lies within the FHA domain of the Chek2 protein (UniProt.org). T172A results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
T205S	missense	no effect - predicted	CHEK2 T205S does not lie within any known functional domains of the Chek2 protein (UniProt.org). T205S results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
T323P	missense	unknown	CHEK2 T323P lies within the protein kinase domain of the Chek2 protein (UniProt.org). T323P results in DNA damage response similar to wild-type Chek2 in a yeast assay (PMID: 22419737), but decreased kinase activity in an in vitro kinase assay (PMID: 16835864), and therefore, its effect on Chek2 protein function is unknown.
T366fs	frameshift	loss of function - predicted	CHEK2 T366fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 366 of 543, likely resulting in premature truncation of the functional protein (UniProt.org). T366fs is predicted to confer a loss of function to the Chek2 protein as demonstrated by loss of kinase activity (PMID: 11053450).
T367fs	frameshift	loss of function	CHEK2 T367fs results in a change in the amino acid sequence of the Chek2 protein beginning at aa 367 of 543, resulting in premature truncation of the functional protein within the kinase domain (UniProt.org). T367fs confers a loss of function to the Chek2 protein as demonstrated by reduced tyrosine phosphorylation in response to DNA damage (PMID: 16982735).
T367Mfs*15	frameshift	loss of function	CHEK2 T367Mfs15 indicates a shift in the reading frame starting at amino acid 367 and terminating 15 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). T367Mfs15 results in reduced tyrosine phosphorylation in response to DNA damage (PMID: 16982735), loss of Kap1 phosphorylation at serine (S)-473 compared to wild-type Chek2 in in vitro assays and in cell culture (PMID: 31050813, PMID: 34903604).
T378I	missense	no effect - predicted	CHEK2 T378I lies within the protein kinase domain of the Chek2 protein (UniProt.org). T378I results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
T387S	missense	loss of function - predicted	CHEK2 T387S lies within the protein kinase domain of the Chek2 protein (UniProt.org). T387S results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
T410fs	frameshift	loss of function	CHEK2 T410fs (corresponds to T367fs in the canonical isoform) results in a change in the amino acid sequence of the Chek2 protein beginning at aa 410 of 586, likely resulting in premature truncation of the functional protein (UniProt.org). T410fs (T367fs) confers a loss of function to the Chek2 protein as demonstrated by reduced tyrosine phosphorylation in response to DNA damage (PMID: 16982735).
T476K	missense	loss of function - predicted	CHEK2 T476K lies within the protein kinase domain of the Chek2 protein (UniProt.org). T476K results in decreased Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
T476M	missense	loss of function	CHEK2 T476M lies within the protein kinase domain of the Chek2 protein (UniProt.org). T476M results in kinase activity similar to wild-type Chek2 in cultured cells but decreased kinase activity in in vitro assays (PMID: 31050813, PMID: 22114986) and decreased DNA damage response in yeast (PMID: 22419737).
T532I	missense	unknown	CHEK2 T532I does not lie within any known functional domains of the Chek2 protein (UniProt.org). T532I has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Nov 2024).
T533A	missense	no effect - predicted	CHEK2 T533A does not lie within any known functional domains of the Chek2 protein (UniProt.org). T533A results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
T59K	missense	loss of function - predicted	CHEK2 T59K does not lie within any known functional domains of the Chek2 protein (UniProt.org). T59K results in a loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.
V109A	missense	unknown	CHEK2 V109A does not lie within any known functional domains of the Chek2 protein (UniProt.org). V109A has been identified in the scientific literature (PMID: 21765476), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
V175A	missense	no effect - predicted	CHEK2 V175A lies within the FHA domain of the Chek2 protein (UniProt.org). V175A results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
V198Ffs*7	frameshift	loss of function - predicted	CHEK2 V198Ffs7 indicates a shift in the reading frame starting at amino acid 198 and terminating seven residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). V198Ffs7 has not been characterized, however, due to the effects of other truncation mutations downstream of V198 resulting in disruption of the protein kinase domain (PMID: 11053450, PMID: 16982735, PMID: 31050813), is predicted to lead to a loss of Chek2 protein function.
V198I	missense	unknown	CHEK2 V198I does not lie within any known functional domains of the Chek2 protein (UniProt.org). V198I has not been characterized in the scientific literature and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
V200A	missense	unknown	CHEK2 V200A does not lie within any known functional domains of the Chek2 protein (UniProt.org). V200A results in intermediate levels of Kap1 phosphorylation and unregulated Chek2 activity upon ionizing radiation in cell culture (PMID: 34903604), but has not been fully biochemically characterized and therefore, its effect on Chek2 protein function is unknown.
V25I	missense	unknown	CHEK2 V25I does not lie within any known functional domains of the Chek2 protein (UniProt.org). V25I has not been characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Nov 2024).
V395L	missense	unknown	CHEK2 V395L lies within the protein kinase domain of the Chek2 protein (UniProt.org). V395L results in a loss of Kap1 phosphorylation at serine (S)-473 in cell culture and in in vitro assays (PMID: 31050813), but similar levels of cell proliferation as compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, its effect on Chek2 protein function is unknown.
W485G	missense	loss of function - predicted	CHEK2 W485G lies within the protein kinase domain of the Chek2 protein (UniProt.org). W485G results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604), and therefore, is predicted to lead to a loss of Chek2 protein function.
W93Gfs*17	frameshift	loss of function - predicted	CHEK2 W93Gfs17 indicates a shift in the reading frame starting at amino acid 93 and terminating 17 residues downstream causing a premature truncation of the 543 amino acid Chek2 protein (UniProt.org). W93Gfs17 is predicted to lead to a loss of Chek2 protein function as indicated by decreased Kap1 phosphorylation in culture (PMID: 34903604).
W93R	missense	loss of function - predicted	CHEK2 W93R does not lie within any known functional domains of the Chek2 protein (UniProt.org). W93R results in decreased cell proliferation compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to lead to a loss of Chek2 protein function.
wild-type	none	no effect	Wild-type CHEK2 indicates that no mutation has been detected within the CHEK2 gene.
Y123C	missense	no effect - predicted	CHEK2 Y123C lies within the FHA domain of the Chek2 protein (UniProt.org). Y123C results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
Y139*	nonsense	loss of function - predicted	CHEK2 Y139* results in a premature truncation of the Chek2 protein at amino acid 139 of 543 (UniProt.org). Y139* results in reduced Chek2 protein and mRNA levels, and decreased p53 phosphorylation and protein levels in patient samples (PMID: 32041497), and therefore, is predicted to lead to a loss of Chek2 protein function.
Y159H	missense	no effect - predicted	CHEK2 Y159H lies within the FHA domain of the Chek2 protein (UniProt.org). Y159H results in cell proliferation similar to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, is predicted to have no effect on Chek2 protein function.
Y327C	missense	unknown	CHEK2 Y327C lies within the protein kinase domain of the Chek2 protein (UniProt.org). Y327C results in a loss of Kap1 phosphorylation at serine (S)-473 in culture and in in vitro assays (PMID: 31050813), however, demonstrates similar cell proliferation as compared to wild-type Chek2 in a yeast assay (PMID: 30851065), and therefore, its effect on Chek2 protein function is unknown.
Y390C	missense	loss of function	CHEK2 Y390C lies within the protein kinase domain of the Chek2 protein (UniProt.org). Y390C confers a loss of function to the Chek2 protein as demonstrated by reduced Kap1 phosphorylation and intermediate Chek2 autophosphorylation upon ionizing radiation in cultured cells (PMID: 34903604), and in the corresponding mouse variant, Y394C, results in decreased p53 phosphorylation upon DNA damage and reduced Cdc25a phosphorylation in cultured cells (PMID: 25619829).
Y390S	missense	loss of function	CHEK2 Y390S lies within the protein kinase domain of the Chek2 protein (UniProt.org). Y390S results in a loss of Chek2 kinase activity in an in vitro kinase assay (PMID: 22114986) and results in reduced Kap1 phosphorylation upon ionizing radiation in culture (PMID: 34903604).
Y404C	missense	unknown	CHEK2 Y404C lies within the protein kinase domain of the Chek2 protein (UniProt.org). Y404C has been identified in sequencing studies (PMID: 29596542, PMID: 36436242), but has not been biochemically characterized and therefore, its effect on Chek2 protein function is unknown (PubMed, Sep 2024).
Y424H	missense	loss of function - predicted	CHEK2 Y424H lies within the protein kinase domain of the Chek2 protein (UniProt.org). Y424H results in Kap1 phosphorylation simliar to wild-type in cultured cells but decreased Kap1 phosphorylation in an in vitro assay (PMID: 31050813) and loss of Chek2-mediated DNA damage response in yeast (PMID: 22419737), and therefore, is predicted to lead to a loss of Chek2 protein function.

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