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Showing 1 to 112 of 112 entries

Gene	Variant	Impact	Protein Effect	Variant Description
PALB2	E3*	nonsense	loss of function - predicted	PALB2 E3* results in a premature truncation of the Palb2 protein at amino acid 3 of 1186 (UniProt.org). E3* has not been characterized however, due to the effects of other truncation mutations downstream of E3 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	P8L	missense	unknown	PALB2 P8L lies within the DNA-binding and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P8L demonstrates subcellular localization, recruitment to DNA damage sites, and Brca1 binding similar to wild-type Palb2 (PMID: 31586400), and leads to homology-directed DNA repair activity similar to wild-type Palb2 in one study (PMID: 31636395), but results in impaired homology-directed DNA repair activity, reduced Rad51 foci formation, and fails to rescue PARP inhibitor sensitivity in PALB2-null cells in another study (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown.
PALB2	L9H	missense	unknown	PALB2 L9H lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L9H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	L24S	missense	loss of function	PALB2 L24S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L24S confers a loss of function to the Palb2 protein as demonstrated by decreased Brca1 binding and Rad51 foci formation (PMID: 31636395), and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31636395, PMID: 31757951, PMID: 33964450).
PALB2	K25*	nonsense	loss of function - predicted	PALB2 K25* results in a premature truncation of the Palb2 protein at amino acid 25 of 1186 (UniProt.org). K25* has not been characterized however, due to the effects of other truncation mutations downstream of K25 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	R34C	missense	unknown	PALB2 R34C lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R34C does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	R34H	missense	unknown	PALB2 R34H lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R34H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	R37C	missense	unknown	PALB2 R37C lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37C results in homology-directed DNA repair activity similar to wild-type in cultured cells in one study (PMID: 31636395), but decreased homology-directed DNA repair activity in another study (PMID: 33811135), and therefore, its effect on Palb2 protein function is unknown.
PALB2	R37S	missense	no effect - predicted	PALB2 R37S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37S results in homology-directed DNA repair similar to wild-type Palb2 in cultured cells (PMID: 31636395, PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	V78I	missense	no effect	PALB2 V78I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). V78I demonstrates homology-directed DNA repair activity comparable to wild-type Palb2 in culture (PMID: 31636395), and results in BRCA2-binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400).
PALB2	P113Qfs*64	frameshift	loss of function - predicted	PALB2 P113Qfs64 indicates a shift in the reading frame starting at amino acid 113 and terminating 64 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). P113Qfs64 has not been characterized however, due to the effects of other truncation mutations downstream of P113 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	R131fs	frameshift	loss of function - predicted	PALB2 R131fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 131 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). R131fs has not been characterized however, due to the effects of other truncation mutations downstream of R131 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	K142Nfs*35	frameshift	loss of function - predicted	PALB2 K142Nfs35 indicates a shift in the reading frame starting at amino acid 142 and terminating 35 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K142Nfs35 has not been characterized however, due to the effects of other truncation mutations downstream of K142 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Q151*	nonsense	loss of function - predicted	PALB2 Q151* results in a premature truncation of the Palb2 protein at amino acid 151 of 1186 (UniProt.org). Q151* has not been characterized however, due to the effects of other truncation mutations downstream of Q151 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	L169I	missense	unknown	PALB2 L169I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L169I demonstrates subcellular localization and recruitment to laser-induced DNA damage sites similar to wild-type Palb2, results in decreased BRCA1 binding in a mammalian two-hybrid assay, reduced RAD51 foci formation and decreased homologous repair activity in one study (PMID: 31586400), but demonstrates homologous repair activity similar to wild-type Palb2 in another study (PMID: 31636395) and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown.
PALB2	R170fs	frameshift	loss of function - predicted	PALB2 R170fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 170 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). R170fs has not been characterized however, due to the effects of other truncation mutations downstream of R170fs (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	P210L	missense	no effect	PALB2 P210L lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). P210L retains homology-directed DNA repair activity in cultured cells (PMID: 31636395, PMID: 31757951), results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400)
PALB2	Q251*	nonsense	loss of function - predicted	PALB2 Q251* results in a premature truncation of the Palb2 protein at amino acid 251 of 1186 (UniProt.org). Q251* results in impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to lead to a loss of Palb2 protein function.
PALB2	S254Ifs*3	frameshift	loss of function - predicted	PALB2 S254Ifs3 indicates a shift in the reading frame starting at amino acid 254 and terminating 3 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S254Ifs3 has not been characterized, however, due to the effects of other truncation mutations downstream of S254 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	N280Tfs*8	frameshift	loss of function - predicted	PALB2 N280Tfs8 indicates a shift in the reading frame starting at amino acid 280 and terminating 8 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N280Tfs8 has not been characterized however, due to the effects of other truncation mutations downstream of N280 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	M296*	nonsense	loss of function - predicted	PALB2 M296* results in a premature truncation of the Palb2 protein at amino acid 296 of 1186 (UniProt.org). M296* has not been characterized however, due to the effects of other truncation mutations downstream of M296 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	I309V	missense	no effect	PALB2 I309V lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). I309V demonstrates homology-directed DNA repair activity similar to wild-type Palb2 in an in vitro assay (PMID: 33964450) and in cultured cells lacking Tp53 (PMID: 31636395).
PALB2	S319Y	missense	no effect - predicted	PALB2 S319Y lies within the DNA-binding, and BRCA1-interacting regions of the Palb2 protein (UniProt.org). S319Y results in reduced BRCA1 binding in a mammalian two-hybrid assay and decreased RAD51 foci formation in culture, but demonstrates subcellular localization, recruitment to laser-induced DNA damage sites (PMID: 31586400), and homologous recombination activity similar to wild-type Palb2 (PMID: 31636395, PMID: 31586400), and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore is predicted to have no effect on Palb2 protein function.
PALB2	L337S	missense	no effect - predicted	PALB2 L337S lies within the DNA-binding region of the Palb2 protein (UniProt.org). L337S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951) and results in homologous recombination activity similar to wild-type in culture (PMID: 33169439), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	N344Tfs*2	frameshift	loss of function - predicted	PALB2 N344Tfs2 indicates a shift in the reading frame starting at amino acid 344 and terminating two residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N344Tfs2 has not been characterized, however, due to the effects of other truncation mutations downstream of N344 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	K346Tfs*13	frameshift	loss of function - predicted	PALB2 K346Tfs13 indicates a shift in the reading frame starting at amino acid 346 and terminating 13 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K346Tfs13 has not been characterized, however, due to the effects of other truncation mutations downstream of K346 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	Q348*	nonsense	loss of function - predicted	PALB2 Q348* results in a premature truncation of the Palb2 protein at amino acid 348 of 1186 (UniProt.org). Q348* has not been characterized, however, due to the effects of other truncation mutations downstream of Q348 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	T351Rfs*4	frameshift	loss of function - predicted	PALB2 T351Rfs4 indicates a shift in the reading frame starting at amino acid 351 and terminating four residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T351Rfs4 has not been characterized, however, due to the effects of other truncation mutations downstream of T351 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	K353Ifs*7	frameshift	loss of function - predicted	PALB2 K353Ifs7 indicates a shift in the reading frame starting at amino acid 353 and terminating seven residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K353Ifs7 has not been characterized, however, due to the effects of other truncation mutations downstream of K353 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	K353Nfs*3	frameshift	loss of function - predicted	PALB2 K353Nfs3 indicates a shift in the reading frame starting at amino acid 353 and terminating three residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K353Nfs3 has not been characterized, however, due to the effects of other truncation mutations downstream of K353 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	P378Lfs*46	frameshift	loss of function - predicted	PALB2 P378Lfs46 indicates a shift in the reading frame starting at amino acid 378 and terminating 46 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). P378Lfs46 has not been characterized, however, due to the effects of other truncation mutations downstream of P378 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	S382I	missense	unknown	PALB2 S382I lies within the DNA-binding region of the Palb2 protein (UniProt.org). S382I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	S387Lfs*14	frameshift	loss of function - predicted	PALB2 S387Lfs14 indicates a shift in the reading frame starting at amino acid 387 and terminating 14 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S387Lfs14 has not been characterized, however, due to the effects of other truncation mutations downstream of S387 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	T397I	missense	unknown	PALB2 T397I lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T397I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	T397S	missense	unknown	PALB2 T397S lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T397S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395) and demonstrates chromatin association similar to wild-type Palb2 in cell culture (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	E407*	nonsense	loss of function - predicted	PALB2 E407* results in a premature truncation of the Palb2 protein at amino acid 407 of 1186 (UniProt.org). E407* has not been characterized, however, due to the effects of other truncation mutations downstream of E407 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Y408H	missense	no effect - predicted	PALB2 Y408H lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). Y408H results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	T413Hfs*11	frameshift	loss of function - predicted	PALB2 T413Hfs11 indicates a shift in the reading frame starting at amino acid 413 and terminating 11 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T413Hfs11 has not been characterized however, due to the effects of other truncation mutations downstream of T413 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	T413K	missense	unknown	PALB2 T413K lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T413K does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	R414*	nonsense	loss of function - predicted	PALB2 R414* results in a premature truncation of the Palb2 protein at amino acid 414 of 1186 (UniProt.org). R414* has not been characterized however, due to the effects of other truncation mutations downstream of R414 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	S417Y	missense	no effect - predicted	PALB2 S417Y lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). S417Y results in reduced chromatin interaction compared to wild-type Palb2 (PMID: 29387807, PMID: 32041954), however, demonstrates Rad51 foci formation and cell survival in response to genotoxic stress similar to wild-type in cultured cells (PMID: 29387807), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	F440fs	frameshift	loss of function - predicted	PALB2 F440fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 440 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). F440fs has not been characterized however, due to the effects of other truncation mutations downstream of F440 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	S474N	missense	unknown	PALB2 S474N lies within the DNA-binding region of the Palb2 protein (UniProt.org). S474N does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	T494Lfs*67	frameshift	loss of function - predicted	PALB2 T494Lfs67 indicates a shift in the reading frame starting at amino acid 494 and terminating 67 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T494Lfs67 has not been characterized, however, due to the effects of other Palb2 truncation mutations downstream of T494 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	K515*	nonsense	loss of function - predicted	PALB2 K515* results in a premature truncation of the Palb2 protein at amino acid 515 of 1186 (UniProt.org). K515* has not been characterized, however, due to the effects of other truncation mutations downstream of K515 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Y551*	nonsense	loss of function	PALB2 Y551* results in a premature truncation of the Palb2 protein at amino acid 551 of 1186 (UniProt.org). Y551* confers a loss of function to the Palb2 protein as demonstrated by loss of Brca2 and Rad51c binding and reduced Rad51 binding in cultured cells (PMID: 24141787), and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951).
PALB2	Q559R	missense	no effect	PALB2 Q559R lies within the DNA-binding region of the Palb2 protein (UniProt.org). Q559R is a common Palb2 polymorphism (PMID: 23977390, PMID: 21165770), results in homologous recombination similar to wild-type Palb2 (PMID: 33169439, PMID: 33964450) and does not demonstrate reduced homology-directed DNA repair activity in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951).
PALB2	S578G	missense	unknown	PALB2 S578G lies within the DNA-binding region of the Palb2 protein (UniProt.org). S578G does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	D595Mfs*4	frameshift	loss of function - predicted	PALB2 D595Mfs4 indicates a shift in the reading frame starting at amino acid 595 and terminating four residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). D595Mfs4 has not been characterized, however, due to the effects of other truncation mutations downstream of D595 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	D616H	missense	unknown	PALB2 D616H does not lie within any known functional domains of the Palb2 protein (UniProt.org). D616H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	L659Qfs*3	frameshift	loss of function - predicted	PALB2 L659Qfs3 indicates a shift in the reading frame starting at amino acid 659 and terminating three residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). L659Qfs3 has not been characterized, however, due to the effects of other truncation mutations downstream of L659 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	L671*	nonsense	loss of function - predicted	PALB2 L671* results in a premature truncation of the Palb2 protein at amino acid 671 of 1186 (UniProt.org). L671* has not been characterized, however, due to the effects of other truncation mutations downstream of L671 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	E672Q	missense	no effect	PALB2 E672Q does not lie within any known functional domains of the Palb2 protein (UniProt.org). E672Q results in homology-directed DNA repair activity similar to wild-type Palb2 in a reporter assay (PMID: 33964450), and homology-directed DNA repair activity similar to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951).
PALB2	N716K	missense	unknown	PALB2 N716K does not lie within any known functional domains of the Palb2 protein (UniProt.org). N716K does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	M723Vfs*21	frameshift	loss of function - predicted	PALB2 M723Vfs21 indicates a shift in the reading frame starting at amino acid 723 and terminating 21 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). M723Vfs21 has not been characterized, however, due to the effects of other truncation mutations downstream of M723 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	T734S	missense	unknown	PALB2 T734S does not lie within any known functional domains of the Palb2 protein (UniProt.org). T734S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	K745E	missense	unknown	PALB2 K745E does not lie within any known functional domains of the Palb2 protein (UniProt.org). K745E does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	S779*	nonsense	loss of function - predicted	PALB2 S779* results in a premature truncation of the Palb2 protein at amino acid 779 of 1186 (UniProt.org). S779* has not been characterized, however, due to the effects of other truncation mutations downstream of S779 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Q790*	nonsense	loss of function - predicted	PALB2 Q790* results in a premature truncation of the Palb2 protein at amino acid 790 of 1186 (UniProt.org). Q790* has not been characterized, however, due to the effects of other truncation mutations downstream of Q790 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	G808*	nonsense	loss of function - predicted	PALB2 G808* results in a premature truncation of the Palb2 protein at amino acid 808 of 1186 (UniProt.org). G808* has not been characterized however, due to the effects of other truncation mutations downstream of G808 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	N821Tfs*25	frameshift	loss of function - predicted	PALB2 N821Tfs25 indicates a shift in the reading frame starting at amino acid 821 and terminating 25 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N821Tfs25 has not been characterized however, due to the effects of other truncation mutations downstream of N821 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	S859*	nonsense	loss of function - predicted	PALB2 S859* results in a premature truncation of the Palb2 protein at amino acid 859 of 1186 (UniProt.org). S859* has not been characterized however, due to the effects of other truncation mutations downstream of S859 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	K862Rfs*9	frameshift	loss of function - predicted	PALB2 K862Rfs9 indicates a shift in the reading frame starting at amino acid 862 and terminating 9 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K862Rfs9 has not been characterized however, due to the effects of other truncation mutations downstream of K862 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	P864S	missense	no effect	PALB2 P864S lies within WD repeat 1 of the Palb2 protein (UniProt.org). P864S results in Brca2 binding, Rad51 foci formation, and recruitment to DNA damage sites similar to wild-type Palb2 in cultured cells (PMID: 31586400), retains homology-directed DNA repair activity in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951), and rescues PARP inhibitor sensitivity in PALB2-null cells (PMID: 31586400).
PALB2	G866V	missense	unknown	PALB2 G866V lies within WD repeat 1 of the Palb2 protein (UniProt.org). G866V does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	D871G	missense	no effect - predicted	PALB2 D871G lies within WD repeat 1 of the Palb2 protein (UniProt.org). D871G results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	W898*	nonsense	loss of function - predicted	PALB2 W898* results in a premature truncation of the Palb2 protein at amino acid 898 of 1186 (UniProt.org). W898* has not been characterized however, due to the effects of other truncation mutations downstream of W898 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	K908fs	frameshift	loss of function - predicted	PALB2 K908fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 908 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). K908fs has not been characterized however, due to the effects of other truncation mutations downstream of K908 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Q921Tfs*7	frameshift	loss of function - predicted	PALB2 Q921Tfs7 indicates a shift in the reading frame starting at amino acid 921 and terminating seven residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). Q921Tfs7 has not been characterized however, due to the effects of other truncation mutations downstream of Q921 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	L931P	missense	unknown	PALB2 L931P lies within WD repeat 2 of the Palb2 protein (UniProt.org). L931P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	L931R	missense	no effect - predicted	PALB2 L931R lies within WD repeat 2 of the Palb2 protein (UniProt.org). L931R results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	V932M	missense	no effect	PALB2 V932M lies within WD repeat 2 of the Palb2 protein (UniProt.org). V932M results in Brca2 binding, Rad51 foci formation, and recruitment to DNA damage sites similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 33964450).
PALB2	L936S	missense	unknown	PALB2 L936S lies within WD repeat 2 of the Palb2 protein (UniProt.org). L936S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown.
PALB2	L939W	missense	unknown	PALB2 L939W lies within WD repeat 2 of the Palb2 protein (UniProt.org). The functional effect of L939W is conflicting, as it has been reported to result in decreased Brca2, Rad51, and Xrcc3 binding in in vitro assays and a modest reduction in homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 24141787), but in another study demonstrates Brca2, Rad51, and Rad51c binding similar to wild-type Palb2 in cultured cells (PMID: 24141787, PMID: 31586400), and homology-directed DNA repair activity similar to wild-type in a reporter assay (PMID: 33964450), and in cultured cells lacking Tp53 (PMID: 27829436, PMID: 31636395, PMID: 31757951), and therefore, its effect on Palb2 protein function is unknown.
PALB2	I944N	missense	loss of function	PALB2 I944N lies within WD repeat 2 of the Palb2 protein (UniProt.org). I944N confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), reduced Brca2 and Rad51 binding, recruitment to DNA damage sites, and Rad51 foci formation, aberrant cytosolic accumulation (PMID: 31636395), and loss of homology-directed DNA repair activity in cultured cells (PMID: 31636395, PMID: 31757951).
PALB2	L947F	missense	loss of function	PALB2 L947F lies within WD repeat 2 of the Palb2 protein (UniProt.org). L947F results in reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400, PMID: 31636395), Palb2 protein accumulation in the cytoplasm, and decreased Rad51 foci formation and foci intensity compared to wild-type protein (PMID: 31586400).
PALB2	S951F	missense	unknown	PALB2 S951F lies within WD repeat 2 of the Palb2 protein (UniProt.org). S951F does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown.
PALB2	Q958P	missense	unknown	PALB2 Q958P lies within WD repeat 2 of the Palb2 protein (UniProt.org). Q958P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	S979Vfs*11	frameshift	loss of function - predicted	PALB2 S979Vfs11 indicates a shift in the reading frame starting at amino acid 979 and terminating 11 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S979Vfs11 has not been characterized however, due to the effects of other truncation mutations downstream of S979 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	G998E	missense	no effect	PALB2 G998E lies within WD repeat 3 of the Palb2 protein (UniProt.org). G998E results in Brca2 binding, Rad51 foci formation, and DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31586400, PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951).
PALB2	E1010*	nonsense	loss of function - predicted	PALB2 E1010* results in a premature truncation of the Palb2 protein at amino acid 1010 of 1186 (UniProt.org). E1010* has not been characterized however, due to the effects of other truncation mutations downstream of E1010 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	V1019A	missense	unknown	PALB2 V1019A lies within WD repeat 4 of the Palb2 protein (UniProt.org). V1019A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	Q1023*	nonsense	loss of function - predicted	PALB2 Q1023* results in a premature truncation of the Palb2 protein at amino acid 1023 of 1186 (UniProt.org). Q1023* has not been characterized however, due to the effects of other truncation mutations downstream of Q1023 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	A1025T	missense	no effect	PALB2 A1025T lies within WD repeat 4 of the palb2 protein (UniProt.org). A1025T results in homologous repair activity similar to wild-type Palb2 in culture (PMID: 31636395, PMID: 33964450), BRCA2-binding similar to wild-type in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400).
PALB2	T1030I	missense	loss of function	PALB2 T1030I lies within WD repeat 4 of the Palb2 protein (UniProt.org). T1030I confers a loss of function to the Palb2 protein as demonstrated by reduced Rad51 and Rad51c binding in in vitro assays (PMID: 24141787), decreased protein stability (PMID: 24141787, PMID: 31757951), reduced Rad51 foci formation, loss of Brca2 binding, and aberrant cytoplasmic localization (PMID: 31586400), and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951).
PALB2	G1043A	missense	loss of function - predicted	PALB2 G1043A lies within WD repeat 4 of the Palb2 protein (UniProt.org). G1043A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), however, results in decreased Brca2 binding, reduced Palb2 recruitment to DNA damage sites, and impaired homology-directed DNA repair activity in cultured cells in another study (PMID: 31586400), and therefore, is predicted to lead to a loss of Palb2 protein function.
PALB2	K1048Rfs*27	frameshift	loss of function - predicted	PALB2 K1048Rfs27 indicates a shift in the reading frame starting at amino acid 1048 and terminating 27 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K1048Rfs27 has not been characterized however, due to the effects of other truncation mutations downstream of K1048 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Q1056*	nonsense	loss of function - predicted	PALB2 Q1056* results in a premature truncation of the Palb2 protein at amino acid 1056 of 1186 (UniProt.org). Q1056* has not been characterized, however, due to the effects of other truncation mutations downstream of Q1056 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	C1060S	missense	unknown	PALB2 C1060S lies within WD repeat 5 of the Palb2 protein (UniProt.org). C1060S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	Y1064C	missense	no effect - predicted	PALB2 Y1064C lies within WD repeat 5 of the Palb2 protein (UniProt.org). Y1064C results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	L1070P	missense	loss of function	PALB2 L1070P lies within WD repeat 5 of the Palb2 protein (UniProt.org). L1070P confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), aberrant cytosolic accumulation and reduced Rad51 foci formation (PMID: 31636395), and intermediate or impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 33964450, PMID: 31636395, PMID: 31757951).
PALB2	E1083D	missense	unknown	PALB2 E1083D lies within WD repeat 5 of the Palb2 protein (UniProt.org). E1083D does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	R1086Efs*9	frameshift	loss of function - predicted	PALB2 R1086Efs9 indicates a shift in the reading frame starting at amino acid 1086 and terminating 9 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). R1086Efs9 has not been characterized, however, due to the effects of other truncation mutations downstream of R1086 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function.
PALB2	I1093T	missense	no effect	PALB2 I1093T lies within WD repeat 5 of the palb2 protein (UniProt.org). I1093T results in homologous repair activity similar to wild-type protein in culture (PMID: 31636395), demonstrates subcellular localization and recruitment to dsDNA damage sites comparable to wild-type Palb2 in culture, results in BRCA2 binding similar to wild-type protein in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400).
PALB2	T1099R	missense	unknown	PALB2 T1099R lies within WD repeat 5 of the Palb2 protein (UniProt.org). T1099R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	S1102R	missense	unknown	PALB2 S1102R lies within WD repeat 5 of the Palb2 protein (UniProt.org). S1102R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	V1103L	missense	unknown	PALB2 V1103L lies within WD repeat 5 of the Palb2 protein (UniProt.org). V1103L does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	V1103M	missense	unknown	PALB2 V1103M lies within WD repeat 5 of the Palb2 protein (UniProt.org). V1103M does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	Y1108fs	frameshift	loss of function - predicted	PALB2 Y1108fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 1108 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). Y1108fs results in impaired homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to lead to a loss of protein function.
PALB2	Q1114H	missense	no effect - predicted	PALB2 Q1114H lies within the RAD51, BRCA2, and POLH-interacting region of the Palb2 protein (UniProt.org). Q1114H results in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to have no effect on protein function.
PALB2	L1119P	missense	unknown	PALB2 L1119P lies within WD repeat 6 of the Palb2 protein (UniProt.org). L1119P results in decreased nuclear localization, Brca2 binding, and recruitment to DNA damage sites and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400), however, demonstrates similar Rad51 foci formation and increased Rad51 foci intensity to wild-type (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, its effect on Palb2 protein function is unknown.
PALB2	G1135E	missense	unknown	PALB2 G1135E lies within WD repeat 6 of the Palb2 protein (UniProt.org). G1135E does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	W1140G	missense	loss of function - predicted	PALB2 W1140G lies within WD repeat 6 of the Palb2 protein (UniProt.org). W1140G does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), however, results in decreased Brca2 binding, reduced Rad51 foci formation, aberrant cytoplasmic localization, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400), and therefore, is predicted to lead to a loss of Palb2 protein function.
PALB2	L1143P	missense	unknown	PALB2 L1143P lies within WD repeat 6 of the Palb2 protein (UniProt.org). The functional effect of L1143P is conflicting, as it has been reported to result in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), however, demonstrates decreased Rad51, Rad51c, and Xrcc3 binding in in vitro assays, and reduced Brca2 and Rad51c binding, decreased Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 24141787), and therefore, its effect on Palb2 protein function is unknown.
PALB2	L1150R	missense	unknown	PALB2 L1150R lies within WD repeat 6 of the Palb2 protein (UniProt.org). L1150R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	W1164C	missense	unknown	PALB2 W1164C lies within WD repeat 7 of the Palb2 protein (UniProt.org). W1164C does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	S1165L	missense	unknown	PALB2 S1165L lies within WD repeat 7 of the Palb2 protein (UniProt.org). S1165L does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown.
PALB2	T1167I	missense	unknown	PALB2 T1167I lies within WD repeat 7 of the Palb2 protein (UniProt.org). T1167I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	G1174R	missense	unknown	PALB2 G1174R lies within WD repeat 7 of the Palb2 protein (UniProt.org). G1174R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
PALB2	I1180T	missense	no effect - predicted	PALB2 I1180T lies within WD repeat 7 of the Palb2 protein (UniProt.org). I1180T results in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function.
PALB2	F1181Lfs*54	frameshift	loss of function - predicted	PALB2 F1181Lfs54 indicates a shift in the reading frame starting at amino acid 1181 and terminating 54 residues downstream, resulting in a premature truncation of the functional protein and extension of the 1186 amino acid Palb2 protein length by 49 amino acids (UniProt.org). F1181Lfs54 has not been characterized, however, due to the effects of other truncation mutations downstream of F1181 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function.
PALB2	Y1183*	nonsense	loss of function	PALB2 Y1183* results in a premature truncation of the Palb2 protein at amino acid 1183 of 1186 (UniProt.org). Y1183* confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PALB2 A1025R	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing PALB2 A1025R were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased cell survival (PMID: 31636395).	31636395
PALB2 I944N	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing PALB2 I944N were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased cell survival (PMID: 31636395).	31636395
PALB2 L1070P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing PALB2 L1070P were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased cell survival (PMID: 31636395).	31636395
PALB2 L24S	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing PALB2 L24S were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased cell survival (PMID: 31636395).	31636395
PALB2 L35P	Advanced Solid Tumor	sensitive	Olaparib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing PALB2 L35P were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased cell survival (PMID: 31636395).	31636395

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