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Gene Symbol TSC2
Synonyms LAM | PPP1R160 | TSC4
Gene Description TSC2, TSC complex subunit 2, forms a complex with Tsc1 and inhibits mTOR pathway signaling, thus regulating cell growth and metabolism (PMID: 27226234). Germline TSC2 inactivating mutations cause tuberous sclerosis complex and somatic TSC2 mutations have been identified in various cancers, including renal cell carcinoma, sarcoma, and breast cancer (PMID: 27226234, PMID: 30303819, PMID: 28860410, PMID: 28027327).
ACMG Incidental List v3.0:
Yes, Tuberous sclerosis complex (PMID: 34012068)
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
7249 16 16p13.3 NM_000548 Tumor suppressor (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1003fs frameshift loss of function TSC2 A1003fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1003 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). A1003fs confers a loss of function to the Tsc2 protein as indicated by increased Ofd1 and p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
A1110T missense unknown TSC2 A1110T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1110T has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
A1141T missense unknown TSC2 A1141T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1141T has been identified in sequencing studies (PMID: 25724664), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
A1258R missense unknown TSC2 A1258R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1258R has been identified in the scientific literature (PMID: 32699558), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
A1294V missense unknown TSC2 A1294V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1294V has been identified in sequencing studies (Journal of Thoracic Oncology, Vol 13, Issue 10, S512-513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
A1297T missense unknown TSC2 A1297T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1297T has been identified in sequencing studies (PMID: 27930734, PMID: 36788092, PMID: 38791144), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A1349Gfs*64 frameshift loss of function - predicted TSC2 A1349Gfs*64 indicates a shift in the reading frame starting at amino acid 1349 and terminating 64 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). A1349Gfs*64 has not been characterized however, due to the effects of other truncation mutations downstream of A1349 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
A1719T missense unknown TSC2 A1719T lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). A1719T has been identified in sequencing studies (PMID: 31308077), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A210T missense unknown TSC2 A210T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A210T has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A272T missense unknown TSC2 A272T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A272T has been identified in sequencing studies (PMID: 29937994), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A289V missense unknown TSC2 A289V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A289V has been identified in sequencing studies (PMID: 26806567), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A460T missense no effect - predicted TSC2 A460T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A460T results in S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 21309039), and therefore, is predicted to have no effect on Tsc2 protein function.
A583T missense unknown TSC2 A583T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A583T has been identified in the scientific literature (PMID: 10205261), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A607E missense loss of function TSC2 A607E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607E results in the loss of repression of Mtorc1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
A607T missense no effect TSC2 A607T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607T demonstrates hamartin interaction, Rheb activation, and inhibition of S6K and S6 phosphorylation to similar levels of wild-type Tsc2 in culture (PMID: 15483652).
A607V missense unknown TSC2 A607V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607V has been identified in sequencing studies (PMID: 26806567, PMID: 26343384), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
A614D missense loss of function TSC2 A614D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A614D confers a loss of function to Tsc2 as demonstrated by decreased Tsc2 phosphorylation and Tsc1 binding in cultured cells (PMID: 11741832), failure to suppress S6k phosphorylation (PMID: 15483652, PMID: 21309039) and stimulate Rheb GTPase activity (PMID: 15483652), and decreased Tsc2 stability in culture (PMID: 21309039).
A678T missense unknown TSC2 A678T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A678T has been identified in sequencing studies (PMID: 29642553, PMID: 31176623, PMID: 35358259), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
A736V missense unknown TSC2 A736V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A736V has been identified in sequencing studies (J Clin Oncol 2021 39:15_suppl, 11538-11538), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
A84T missense no effect - predicted TSC2 A84T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A84T results in Tsc2 splicing similar to wild-type Tsc2 in an in vitro assay and complex formation with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
A86T missense unknown TSC2 A86T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A86T has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
amp none no effect TSC2 amplification indicates an increased number of copies of the TSC2 gene. However, the mechanism causing the increase is unspecified.
C256Y missense unknown TSC2 C256Y lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). C256Y has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
C696Y missense loss of function TSC2 C696Y does not lie within any known functional domains of the Tsc2 protein (UniProt.org). C696Y confers a loss of function to Tsc2 as demonstrated by decreased suppression of S6k phosphorylation (PMID: 15483652, PMID: 21309039), failure to stimulate Rheb GTPase activity (PMID: 15483652), and decreased Tsc2 stability in culture (PMID: 21309039).
C811R missense unknown TSC2 C811R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). C811R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
C900* nonsense loss of function - predicted TSC2 C900* results in a premature truncation of the Tsc2 protein at amino acid 900 of 1807 (UniProt.org). C900* has not been characterized however, due to the effects of other truncation mutations downstream of C900 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
D1004N missense unknown TSC2 D1004N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1004N has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
D1004Y missense unknown TSC2 D1004Y does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1004Y has been identified in sequencing studies (PMID: 30556601), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
D1406N missense unknown TSC2 D1406N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1406N has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
D1512A missense loss of function TSC2 D1512A (corresponding to D1535A in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1512A results in a loss of Tsc2 protein function as indicated by increased phosphorylation of S6k in cultured cells (PMID: 18854862, PMID: 37311496).
D1590N missense unknown TSC2 D1590N lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1590N has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
D1598fs frameshift loss of function - predicted TSC2 D1598fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1598 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). D1598fs has not been characterized however, due to the effects of other truncation mutations downstream of D1598 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
D1656N missense no effect TSC2 D1656N lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1656N results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay (PMID: 32502382), inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382, PMID: 31799751), and interaction with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751).
D1656Y missense no effect - predicted TSC2 D1656Y lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1656Y results in noncanonical splicing of Tsc2 in cultured cells (PMID: 31799751), but protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay (PMID: 32502382), inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382, PMID: 31799751), and interaction with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
D1690fs frameshift loss of function - predicted TSC2 D1690fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1690 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). D1690fs has not been characterized however, due to the effects of other truncation mutations downstream of D1690 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
D514Pfs*74 frameshift loss of function - predicted TSC2 D514Pfs*74 indicates a shift in the reading frame starting at amino acid 514 and terminating 74 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). D514Pfs*74 has not been characterized however, due to the effects of other truncation mutations downstream of D514 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
del deletion loss of function TSC2 del indicates a deletion of the TSC2 gene.
E114* nonsense loss of function - predicted TSC2 E114* results in a premature truncation of the Tsc2 protein at amino acid 114 of 1807 (UniProt.org). E114* has not been characterized however, due to the effects of other truncation mutations downstream of E114 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
E1343D missense unknown TSC2 E1343D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). E1343D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
E134K missense unknown TSC2 E134K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E134K has been identified in the scientific literature (PMID: 24755471, PMID: 29212165), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
E138* nonsense loss of function - predicted TSC2 E138* results in a premature truncation of the Tsc2 protein at amino acid 138 of 1807 (UniProt.org). E138* has not been characterized however, due to the effects of other truncation mutations downstream of E138 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
E379G missense unknown TSC2 E379G lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E379G has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
E546K missense unknown TSC2 E546K does not lie within any known functional domains of the Tsc2 protein (UniProt.org). E546K has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
E652fs frameshift loss of function - predicted TSC2 E652fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 652 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). E652fs has not been characterized however, due to the effects of other truncation mutations downstream of E652 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
E74K missense unknown TSC2 E74K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E74K has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
E96* nonsense loss of function - predicted TSC2 E96* results in a premature truncation of the Tsc2 protein at amino acid 96 of 1807 (UniProt.org). E96* has not been characterized however, due to the effects of other truncation mutations downstream of E96 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
F1510del deletion unknown TSC2 F1510del results in the deletion of an amino acid of the Tsc2 protein at amino acid 1510 (UniProt.org). F1510del has been identified in the scientific literature (PMID: 35732329, PMID: 33935721, PMID: 34160418 ), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
F15V missense unknown TSC2 F15V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). F15V has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
F1668L missense loss of function - predicted TSC2 F1668L lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). F1668L results in protein stability and inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells but results in a loss of catalytic activity in an in vitro assay (PMID: 32502382), and therefore, is predicted to lead to a loss of Tsc2 protein function.
F452L missense unknown TSC2 F452L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). F452L has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
F615S missense loss of function - predicted TSC2 F615S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). F615S activates Rheb GTPase to similar levels of wild-type Tsc2 (PMID: 15483652) but results in decreased suppression of S6k phosphorylation (PMID: 15483652, PMID: 21309039), and reduced Tsc2 stability in culture (PMID: 21309039), and therefore, is predicted to lead to a loss of Tsc2 protein function.
G1055D missense unknown TSC2 G1055D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1055D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
G1354D missense unknown TSC2 G1354D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1354D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
G1416D missense no effect - predicted TSC2 G1416D (corresponding to G1439D in the canonical isoform) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1416D results in Tsc1, Tsc2, and S6k expression (PMID: 21309039) and inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
G1494D missense unknown TSC2 G1494D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1494D has been identified in sequencing studies (PMID: 24121792, PMID: 33115932), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
G150K missense unknown TSC2 G150K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G150K has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
G1544V missense loss of function TSC2 G1544V (corresponding to G1567V in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). G1544V results in the loss of repression of MTORC1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
G1604C missense unknown TSC2 G1604C lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). G1604C has been identified in sequencing studies (PMID: 33727259), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, May 2024).
G1791S missense unknown TSC2 G1791S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1791S has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
G294E missense loss of function TSC2 G294E lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G294E results in increased expression of Mcp-1 compared to wild-type Tsc2 in cell culture (PMID: 16129702) and failure to bind TSC1 in vitro (PMID: 11741833, PMID: 23955302).
G305* nonsense loss of function - predicted TSC2 G305* results in a premature truncation of the Tsc2 protein at amino acid 305 of 1807 (UniProt.org). G305* has not been characterized however, due to the effects of other truncation mutations downstream of G305 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
G440S missense unknown TSC2 G440S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G440S has been identified in sequencing studies (PMID: 10205261, PMID: 34445161), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
G62E missense no effect - predicted TSC2 G62E lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G62E results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
G654Efs*45 frameshift loss of function - predicted TSC2 G654Efs*45 indicates a shift in the reading frame starting at amino acid 654 and terminating 45 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). G654Efs*45 has not been characterized however, due to the effects of other truncation mutations downstream of G654 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
G676S missense unknown TSC2 G676S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G676S has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
H1135R missense unknown TSC2 H1135R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). H1135R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
H1617Y missense loss of function TSC2 H1617Y (corresponding to H1640Y in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). H1617Y results in the loss of repression of Mtorc1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
H1718P missense loss of function TSC2 H1718P lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). H1718P confers a loss of function to the Tsc2 protein as indicated by increased Ofd1 and p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
H1746_R1751del deletion loss of function TSC2 H1746_R1751del (also referred to as R1743_K1748del) results in the deletion of six amino acids in the Rap-GAP domain of the Tsc2 protein from amino acids 1746 to 1751 (UniProt.org). H1746_R1751del confers a loss of function on the Tsc2 protein as indicated by destabilization of the TSC1-TSC2 complex (PMID: 21309039), increased phosphorylation of S6, potentially resulting in hyperactivation of Mtorc1, and a decrease in Akt phosphorylation in cultured cells. (PMID: 31591157).
H597N missense unknown TSC2 H597N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). H597N has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
I1197F missense loss of function - predicted TSC2 I1197F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). I1197F results in interaction with Tsc1 similar to wild-type Tsc2, but decreased inhibition of mTorc1 activity as indicated by reduced inhibition of S6k phosphorylation in cultured cells (PMID: 31799751), and therefore, is predicted to lead to a loss of Tsc2 protein function.
I1561Hfs*5 frameshift loss of function - predicted TSC2 I1561Hfs*5 indicates a shift in the reading frame starting at amino acid 1561 and terminating 5 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). I1561Hfs*5 has not been characterized however, due to the effects of other truncation mutations downstream of I1561 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
I365del deletion loss of function TSC2 I365del results in the deletion of an amino acid in the Tsc2 protein at amino acid 365 (UniProt.org). I365del confers a loss of function on Tsc2, as demonstrated by abolished tuberin-hamartin binding in a yeast assay (PMID: 11741833), and failure to inhibit Mcp-1 production in cell culture (PMID: 16129702).
I427_S428del deletion unknown TSC2 I427_S428del results in the deletion of two amino acids of the Tsc2 protein from amino acid 427 to 428 (UniProt.org). I427_S428del has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
inact mut unknown loss of function TSC2 inact mut indicates that this variant results in a loss of function of the Tsc2 protein. However, the specific amino acid change has not been identified.
K1065E missense unknown TSC2 K1065E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). K1065E has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
K1585R missense unknown TSC2 K1585R lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). K1585R has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
K347Efs*36 frameshift loss of function - predicted TSC2 K347Efs*36 indicates a shift in the reading frame starting at amino acid 347 and terminating 36 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). K347Efs*36 results in increased phosphorylation of S6k1 and Stat3 in cultured cells (PMID: 31454656), and therefore, is predicted to lead to a loss of Tsc2 protein function.
K599M missense unknown TSC2 K599M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). K599M results in chaperone function, Tsc2 phosphorylation, Tsc1 binding and subcellular localization (PMID: 11741832), S6k phosphorylation (PMID: 15483652, PMID: 21309039), and Tsc1 and Tsc2 stability similar to wild-type Tsc2 (PMID: 21309039), but results in decreased Tsc2 acetylation, reduced response to Tsc2 acetylation-induced mTORC1 activation, and decreased cell proliferation in culture (PMID: 27542907), and therefore, its effect on Tsc2 protein function is unknown.
L1137F missense unknown TSC2 L1137F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1137F has not been characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
L1198M missense unknown TSC2 L1198M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1198M has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
L1216I missense unknown TSC2 L1216I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1216I has not been characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
L1504F missense unknown TSC2 L1504F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1504F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
L1597Rfs*4 frameshift loss of function - predicted TSC2 L1597Rfs*4 indicates a shift in the reading frame starting at amino acid 1597 and terminating 4 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). L1597Rfs*4 has not been characterized however, due to the effects of other truncation mutations downstream of L1597 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
L1750Afs*25 frameshift loss of function - predicted TSC2 L1750Afs*25 indicates a shift in the reading frame starting at amino acid 1750 and terminating 25 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). L1750Afs*25 results in increased mTorc1 signaling in culture (PMID: 22903760), and therefore, is predicted to lead to a loss of Tsc2 protein function.
L204V missense unknown TSC2 L204V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L204V has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
L264Wfs*73 frameshift loss of function - predicted TSC2 L264Wfs*73 indicates a shift in the reading frame starting at amino acid 264 and terminating 73 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). L264Wfs*73 has not been characterized however, due to the effects of other truncation mutations downstream of L264 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
L369P missense loss of function TSC2 L369P lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L369P fails to inhibit mTorc1 activity as indicated by reduced inhibition of S6k phosphorylation and results in decreased binding to Tsc1 in cultured cells (PMID: 31799751).
L369R missense unknown TSC2 L369R lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L369R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
L493V missense unknown TSC2 L493V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L493V results in decreased interaction with Tsc1 in cultured cells, and noncanonical Tsc2 splicing in an in vitro assay, but results in Mtorc1 inhibition similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, its effect on Tsc2 protein function is unknown.
L604P missense unknown TSC2 L604P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L604P has been identified in sequencing studies (PMID: 26469692), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
L688M missense unknown TSC2 L688M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L688M has been identified in sequencing studies (PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
L916P missense loss of function - predicted TSC2 L916P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L916P results in interaction with Tsc1 similar to wild-type Tsc2, but fails to inhibit Mtorc1 activity as indicated by failure to inhibit S6k phosphorylation in cultured cells (PMID: 31799751), and therefore, is predicted to lead to a loss of Tsc2 protein function.
loss unknown loss of function TSC2 loss indicates loss of the TSC2 gene, mRNA, and protein.
M168I missense unknown TSC2 M168I lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M168I has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
M1691T missense unknown TSC2 M1691T lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). M1691T has been identified in sequencing studies (PMID: 27882345), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
M280T missense loss of function TSC2 M280T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M280T results in disruption of the Tsc complex function as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
M286V missense no effect TSC2 M286V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M286V results in the expression of Mcp-1 similar to wild-type Tsc2 in cell culture (PMID: 16129702), binds Tsc1 similar to wild-type Tsc2 in an in vitro assay (PMID: 11741833), and results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in an in vitro assay (PMID: 32555378).
M649I missense unknown TSC2 M649I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). M649I has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
mutant unknown unknown TSC2 mutant indicates an unspecified mutation in the TSC2 gene.
N1064Kfs*104 frameshift loss of function - predicted TSC2 N1064Kfs*104 indicates a shift in the reading frame starting at amino acid 1064 and terminating 104 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). N1064Kfs*104 has not been characterized however, due to the effects of other truncation mutations downstream of N1064 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
N1214I missense unknown TSC2 N1214I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). N1214I has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
N1224I missense unknown TSC2 N1224I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). N1224I has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
N1643H missense loss of function TSC2 N1643H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). N1643H demonstrates protein stability similar to wild-type Tsc2 in an in vitro assay, but fails to inhibit Mtorc1 signaling and results in a loss of catalytic activity in an in vitro assay (PMID: 32502382), and therefore, results in a loss of Tsc2 protein function.
N1707S missense no effect - predicted TSC2 N1707S lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). N1707S results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay and inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382), and therefore, is predicted to have no effect on Tsc2 protein function.
N275del deletion loss of function TSC2 N275del results in the deletion of an amino acid in the TSC1-interacting region of the Tsc1 protein at amino acid 275 (UniProt.org). N275del results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
N525S missense no effect TSC2 N525S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). N525S results in phosphorylation by Pkb, Tsc2 and S6 phosphorylation, Tsc1 binding, Rheb GTPase activity (PMID: 15483652), chaperone function, and Tsc1 subcellular localization similar to wild-type Tsc2 in culture (PMID: 11741832).
P1092L missense unknown TSC2 P1092L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1092L has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
P1176fs frameshift loss of function - predicted TSC2 P1176fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1176 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). P1176fs has not been characterized however, due to the effects of other truncation mutations downstream of P1176 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
P1292A missense no effect - predicted TSC2 P1292A (corresponding to P1315A in the canonical isoform) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1292A results in Tsc1, Tsc2, and S6k expression (PMID: 21309039) and inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
P1497H missense unknown TSC2 P1497H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1497H has been identified in the scientific literature (PMID: 35965503), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, May 2024).
P1521T missense unknown TSC2 P1521T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1521T has been identified in the scientific literature (PMID: 31978326), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
P1675R missense unknown TSC2 P1675R lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). P1675R has been identified in sequencing studies (PMID: 33727259), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, May 2024).
P1770S missense unknown TSC2 P1770S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1770S has been identified in sequencing studies (PMID: 24265153), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
P237L missense unknown TSC2 P237L lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). P237L has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
P28fs frameshift loss of function - predicted TSC2 P28fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 28 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). P28fs has not been characterized however, due to the effects of other truncation mutations downstream of P28 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
P674S missense unknown TSC2 P674S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P674S has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
Q112* nonsense loss of function - predicted TSC2 Q112* results in a premature truncation of the Tsc2 protein at amino acid 112 of 1807 (UniProt.org). Q112* has not been characterized however, due to the effects of other truncation mutations downstream of Q112 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
Q1178* nonsense loss of function - predicted TSC2 Q1178* results in a premature truncation of the Tsc2 protein at amino acid 1178 of 1807 (UniProt.org). Q1178* has not been characterized however, due to the effects of other truncation mutations downstream of Q1178 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
Q1192* nonsense loss of function - predicted TSC2 Q1192* results in a premature truncation of the Tsc2 protein at amino acid 1192 of 1807 (UniProt.org). Q1192* has not been characterized however, due to the effects of other truncation mutations downstream of Q1192 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
Q1503* nonsense loss of function - predicted TSC2 Q1503* results in a premature truncation of the Tsc2 protein at amino acid 1503 of 1807 (UniProt.org). Q1503* has not been characterized however, due to the effects of other truncation mutations downstream of Q1503 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
Q200fs frameshift loss of function - predicted TSC2 Q200fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 200 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). Q200fs has not been characterized however, due to the effects of other truncation mutations downstream of Q200 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
Q325* nonsense loss of function - predicted TSC2 Q325* results in a premature truncation of the Tsc2 protein at amino acid 325 of 1807 (UniProt.org). Q325* has not been characterized however, due to the effects of other truncation mutations downstream of Q325 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
Q371H missense unknown TSC2 Q371H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). Q371H has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513, PMID: 25801821), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
Q373P missense no effect - predicted TSC2 Q373P lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). Q373P results in expression of Tsc1, Tsc2, and S6k (PMID: 21309039) and inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862, PMID: 21309039), and therefore, is predicted to have no effect on Tsc2 protein function.
Q417* nonsense loss of function - predicted TSC2 Q417* results in a premature truncation of the Tsc2 protein at amino acid 417 of 1807 (UniProt.org). Q417* has not been characterized however, due to the effects of other truncation mutations downstream of Q417 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
Q572H missense unknown TSC2 Q572H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). Q572H has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
Q785* nonsense loss of function - predicted TSC2 Q785* results in a premature truncation of the Tsc2 protein at amino acid 785 of 1807 (UniProt.org). Q785* has not been characterized however, due to the effects of other truncation mutations downstream of Q785 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
Q90* nonsense loss of function - predicted TSC2 Q90* results in a premature truncation of the Tsc2 protein at amino acid 90 of 1807 (UniProt.org). Q90* has not been characterized however, due to the effects of other truncation mutations downstream of Q90 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
R1032Q missense unknown TSC2 R1032Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1032Q has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R1138* nonsense loss of function - predicted TSC2 R1138* results in a premature truncation of the Tsc2 protein at amino acid 1138 of 1807 (UniProt.org). R1138* has not been characterized however, due to the effects of other truncation mutations downstream of R1138 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
R115H missense unknown TSC2 R115H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R115H has been identified in sequencing studies (PMID: 29312904), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R1200P missense loss of function - predicted TSC2 R1200P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1200P results in decreased mTorc1 inhibition (PMID: 29308833), and therefore, is predicted to lead to a loss of Tsc2 protein function.
R1268G missense unknown TSC2 R1268G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1268G has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R1329P missense unknown TSC2 R1329P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1329P has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R1361Q missense unknown TSC2 R1361Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1361Q has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R1409G missense no effect - predicted TSC2 R1409G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1409G results in canonical splicing in an in vitro assay, and leads to Tsc1 interaction and Mtorc1 inhibition similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
R1459* nonsense loss of function - predicted TSC2 R1459* results in a premature truncation of the Tsc2 protein at amino acid 1459 of 1807 (UniProt.org). R1459* has not been characterized however, due to the effects of other truncation mutations downstream of R1459 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
R1580W missense no effect - predicted TSC2 R1580W lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1580W results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay and inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382), and therefore, is predicted to have no effect on Tsc2 protein function.
R1639H missense unknown TSC2 R1639H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1639H has been identified in sequencing studies (PMID: 22895193, PMID: 32221016), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R1720Q missense loss of function TSC2 R1720Q (corresponding to R1743Q in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1720Q results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
R1729H missense unknown TSC2 R1729H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1729H has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R1743W missense loss of function TSC2 R1743W lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1743W results in the loss of repression of mTORC1 as demonstrated by increased phosphorylation of S6K1 and 4E-BP1, reduced intrinsic GTPase activity, and PEX5 association and peroxisomal localization compared to wild-type Tsc2 protein in in-vitro assays (PMID: 23955302).
R1745C missense unknown TSC2 R1745C lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1745C has been identified in sequencing studies (PMID: 29669935, PMID: 24755471, PMID: 34839264), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R1745H missense unknown TSC2 R1745H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1745H has been identified in sequencing studies (PMID: 35300216, PMID: 37994105), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R1795C missense no effect TSC2 R1795C (corresponding to R1772C in isoform 4) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1795C demonstrates activity similar to wild-type Tsc2 in in vitro assays (PMID: 21309039, PMID: 18302728).
R308W missense loss of function TSC2 R308W lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R308W fails to inhibit Mtorc1 activity as indicated by reduced inhibition of S6k phosphorylation and results in decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
R367Q missense no effect - predicted TSC2 R367Q lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R367Q results in the expression of Mcp-1 similar to wild-type Tsc2 in cell culture (PMID: 16129702) and binds TSC1 similar to wild-type in an in vitro assay (PMID: 11741833), and therefore, is predicted to have no effect on Tsc2 protein function.
R458* nonsense loss of function - predicted TSC2 R458* results in a premature truncation of the Tsc2 protein at amino acid 458 of 1807 (UniProt.org). R458* has not been characterized however, due to the effects of other truncation mutations downstream of R458 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
R505* nonsense loss of function - predicted TSC2 R505* results in a premature truncation of the Tsc2 protein at amino acid 505 of 1807 (UniProt.org). R505* has not been characterized however, due to the effects of other truncation mutations downstream of R505 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
R537C missense unknown TSC2 R537C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R537C has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R57H missense unknown TSC2 R57H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R57H results in reduced expression of Tsc1 and Tsc2, however, also demonstrates increased S6k phosphorylation compared to wild-type Tsc2 in cultured cells (PMID: 21309039), and therefore, its effect on Tsc2 protein function is unknown.
R585H missense unknown TSC2 R585H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R585H has been identified in sequencing studies (PMID: 27149842, PMID: 22490766, PMID: 33067351) but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R611Q missense loss of function TSC2 R611Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R611Q fails to inhibit Mtorc1 signaling in cultured cells (PMID: 31799751, PMID: 26703369, PMID: 18854862), and results in reduced interaction with Tsc1 in cultured cells (PMID: 26703369, PMID: 18854862).
R611W missense loss of function TSC2 R611W does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R611W confers a loss of function to Tsc2 as demonstrated by loss of chaperone function, decreased Tsc1 binding, and decreased Tsc2 phosphorylation in cultured cells (PMID: 11741832).
R622W missense loss of function TSC2 R622W does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R622W confers a loss of function to the Tsc2 protein as it results in loss of Tsc1 binding and decreased Tsc2 GAP activity in cell culture (PMID: 20633017).
R718H missense unknown TSC2 R718H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R718H has been identified in sequencing studies (PMID: 25233892, PMID: 27149842, PMID: 38041139), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
R751* nonsense loss of function - predicted TSC2 R751* results in a premature truncation of the Tsc2 protein at amino acid 751 of 1807 (UniProt.org). R751* has not been characterized however, due to the effects of other truncation mutations downstream of R751 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
R901C missense loss of function TSC2 R901C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R901C confers a loss of function to the Tsc2 protein, as it results in increased mTOR pathway activation, with elevated phosphorylation of S6k and 4Ebp1, and decreased binding to Tsc1 compared to wild-type Tsc2 in culture (PMID: 36229297).
R901H missense unknown TSC2 R901H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R901H has been identified in sequencing studies (PMID: 29899868, PMID: 28188106), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R905fs frameshift loss of function TSC2 R905fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 905 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). R905fs confers a loss of function to the Tsc2 protein as indicated by increased p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
R905Q missense loss of function - predicted TSC2 R905Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R905Q results in chaperone function, Tsc2 phosphorylation, Tsc1 binding, and Tsc1 subcellular localization similar to wild-type Tsc2 (PMID: 11741832) but results in decreased suppression of S6k phosphorylation (PMID: 15483652, PMID: 21309039), failure to activate Rheb GTPase activity (PMID: 15483652), and decreased Tsc2 stability in culture (PMID: 16464865, PMID: 21309039), and therefore, is predicted to lead to a loss of Tsc2 protein function.
R978H missense unknown TSC2 R978H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R978H has been identified in sequencing studies (PMID: 25822088, PMID: 22343534), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
R98W missense loss of function TSC2 R98W lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R98W results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
S1036F missense unknown TSC2 S1036F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1036F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S1045F missense loss of function - predicted TSC2 S1045F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1045F retains the ability to form TSC complex, but results in reduced ability to inhibit S6k phosphorylation in culture (PMID: 31799751), and therefore, is predicted to lead to a loss of Tsc2 protein function.
S1085fs frameshift loss of function - predicted TSC2 S1085fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1085 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). S1085fs has not been characterized however, due to the effects of other truncation mutations downstream of S1085 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
S1090C missense unknown TSC2 S1090C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1090C has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
S1130A missense unknown TSC2 S1130A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1130A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
S1132A missense unknown TSC2 S1132A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1132A results in phosphorylated Tsc2 levels similar to wild-type (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
S1220T missense unknown TSC2 S1220T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1220T has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S1221L missense unknown TSC2 S1221L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1221L has been identified in sequencing studies (PMID: 29316426), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
S1410L missense no effect - predicted TSC2 S1410L (corresponds to S1433L in the canonical isoform) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1410L results in Tsc1, Tsc2, and S6k expression (PMID: 21309039) and inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
S1420A missense unknown TSC2 S1420A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1420A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
S1431L missense unknown TSC2 S1431L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1431L has been identified in sequencing studies (PMID: 27170661), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S1524L missense unknown TSC2 S1524L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1524L has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S1568C missense unknown TSC2 S1568C lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). S1568C results in inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells, but leads to altered Tsc2 protein folding (PMID: 32502382), and therefore, its effect on Tsc2 protein function is unknown.
S1723* nonsense loss of function - predicted TSC2 S1723* results in a premature truncation of the Tsc2 protein at amino acid 1723 of 1807 (UniProt.org). S1723* has not been characterized however, due to the effects of other truncation mutations downstream of S1723 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
S1798A missense loss of function - predicted TSC2 S1798A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1798A results in a loss of phosphorylation by Pim2 and subsequently, prevents Pim2 from relieving suppression of phosphorylated-S6RP compared to wild-type Tsc2 in in vitro assays (PMID: 23818547), and therefore, is predicted to lead to a loss of Tsc2 protein function.
S1798F missense unknown TSC2 S1798F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1798F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S311F missense unknown TSC2 S311F lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). S311F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S554L missense unknown TSC2 S554L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S554L has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
S641R missense unknown TSC2 S641R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S641R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S932N missense unknown TSC2 S932N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S932N has been identified in sequencing studies (PMID: 25233892) but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
S939A missense unknown TSC2 S939A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). The functional effect of S939A is conflicting, as it results in Tsc2 phosphorylation levels, GAP activity towards Rheb, and binding to 14-3-3 and Hamartin similar to wild-type Tsc2 in vitro, however, also demonstrates altered cellular localization, reduced S6k phosphorylation, increased mitotic cell number (PMID: 23818547, PMID: 16636147, PMID: 12582162, PMID: 30629673), diminished binding to 14-3-3 (PMID: 20412061), and loss of phosphorylation and activation of Mtorc1 upon translation inhibition (PMID: 30684133), and therefore, its effect on Tsc2 protein function is unknown.
S981A missense unknown TSC2 S981A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). The functional effect of S981A is conflicting, as it results in Tsc2 phosphorylation levels and GAP activity towards Rheb similar to wild-type, however, also demonstrates altered cellular localization and reduced S6k phosphorylation in culture cells (PMID: 23818547, PMID: 16636147), and therefore, its effect on Tsc2 protein function is unknown.
T1059Nfs*109 frameshift loss of function - predicted TSC2 T1059Nfs*109 indicates a shift in the reading frame starting at amino acid 1059 and terminating 109 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). T1059Nfs*109 has not been characterized however, due to the effects of other truncation mutations downstream of T1059 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
T1068I missense loss of function TSC2 T1068I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1068I results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
T1075I missense no effect - predicted TSC2 T1075I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1075I results in Tsc1, Tsc2, and S6k expression (PMID: 21309039) and inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862, PMID: 21309039), and therefore, is predicted to have no effect on Tsc2 protein function.
T1206A missense unknown TSC2 T1206A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1206A has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
T1462A missense no effect - predicted TSC2 T1462A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1462A results in Tsc2 phosphorylation, binding to 14-3-3, and cellular localization similar to wild-type Tsc2 in culture (PMID: 23818547, PMID: 16636147, PMID: 20412061), and therefore, is predicted to have no effect on Tsc2 protein function.
T147K missense loss of function TSC2 T147K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). T147K results in disruption of the Tsc complex function as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
T993A missense unknown TSC2 T993A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T993A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
V1034I missense unknown TSC2 V1034I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1034I has been identified in sequencing studies (PMID: 27930734), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V1067E missense loss of function - predicted TSC2 V1067E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1067E results in increased Torc1 activity and decreased Tsc2 expression compared to wild-type Tsc2 in culture (PMID: 29632054), and therefore, is predicted to lead to a loss of Tsc2 protein function.
V1144M missense unknown TSC2 V1144M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1144M has been identified in the scientific literature (PMID: 22903760), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V1199G missense loss of function TSC2 V1199G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1199G results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
V1547I missense loss of function TSC2 V1547I lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1547I results in decreased GAP activity of Tsc2 and increased phosphorylation of S6K in cell culture (PMID: 28215400).
V1623G missense loss of function TSC2 V1623G (corresponding to V1646G in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1623G results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
V1646G missense loss of function TSC2 V1646G lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1646G results in destabilization of the Tsc2 protein in an in vitro assay and fails to inhibit mTorc1 signaling in cultured cells (PMID: 32502382), and therefore, results in a loss of Tsc2 protein function.
V1703M missense unknown TSC2 V1703M lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1703M has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2024).
V225M missense unknown TSC2 V225M lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). V225M has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V241I missense unknown TSC2 V241I lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). V241I has been identified in the scientific literature (PMID: 32193183), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jul 2024).
V299fs frameshift loss of function - predicted TSC2 V299fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 299 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). V299fs has not been characterized however, due to the effects of other truncation mutations downstream of V299 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
V461M missense unknown TSC2 V461M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V461M has been identified in sequencing studies (PMID: 28422758, PMID: 22895193, PMID: 33609721), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V472M missense unknown TSC2 V472M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V472M has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V504D missense loss of function TSC2 V504D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V504D fails to inhibit Mtorc1 activity as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
V550G missense unknown TSC2 V550G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V550G has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V679M missense unknown TSC2 V679M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V679M has been identified in sequencing studies (PMID: 22895193, PMID: 29316426), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).
V692I missense unknown TSC2 V692I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V692I has not been characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2024).
V769E missense loss of function TSC2 V769E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V769E confers a loss of function to Tsc2 as demonstrated by decreased Tsc2 phosphorylation and Tsc1 binding in cultured cells (PMID: 11741832), decreased suppression of S6k phosphorylation (PMID: 15483652, PMID: 21309039), failure to stimulate Rheb GTPase activity (PMID; 15483652), and reduced Tsc2 stability in culture (PMID: 21309039).
V909Cfs*6 frameshift loss of function - predicted TSC2 V909Cfs*6 indicates a shift in the reading frame starting at amino acid 909 and terminating 6 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). V909Cfs*6 results in increased phosphorylation of S6k1 and Stat3 in cultured cells (PMID: 31454656), and therefore, is predicted to lead to a loss of Tsc2 protein function.
W1208* nonsense loss of function - predicted TSC2 W1208* results in a premature truncation of the Tsc2 protein at amino acid 1208 of 1807 (UniProt.org). W1208* has not been characterized however, due to the effects of other truncation mutations downstream of W1208 (PMID: 22903760), is predicted to lead to a loss of Tsc2 protein function.
W304Ffs*27 frameshift loss of function - predicted TSC2 W304Ffs*27 indicates a shift in the reading frame starting at amino acid 304 and terminating 27 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). W304Ffs*27 has not been characterized however, due to the effects of other truncation mutations downstream of W304 (PMID: 22903760, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
wild-type none no effect Wild-type TSC2 indicates that no mutation has been detected within the TSC2 gene.
Y1608D missense unknown TSC2 Y1608D lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). Y1608D has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2024).