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| Gene Symbol | MSH6 | ||||||||||
| Synonyms | GTBP | GTMBP | HNPCC5 | HSAP | LYNCH5 | MMRCS3 | MSH-6 | p160 | ||||||||||
| Gene Description | MSH6, mutS homolog 6, binds with Msh2 to form the MutS-alpha complex, which functions in initiation of the DNA mismatch repair system (PMID: 23391514) and is associated with microsatellite instability (MSI) (PMID: 30121009). Mutations in MSH6 are associated with susceptibility to colon cancer and endometrial cancer (PMID: 20028993), and germline MSH6 mutations are associated with Lynch (Hereditary Nonpolyposis Colorectal Cancer) syndrome (PMID: 15528792). | ||||||||||
| ACMG Incidental List v3.0: |
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| Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|
| A1021D | missense | unknown | MSH6 A1021D lies within the lever domain of the Msh6 protein (PMID: 17531815). A1021D demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| A1055P | missense | loss of function - predicted | MSH6 A1055P lies within the lever domain of the Msh6 protein (PMID: 17531815). A1055P demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| A1064T | missense | unknown | MSH6 A1064T lies within MutS domain 3 of the Msh6 protein (PMID: 23621914). A1064T does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| A1204E | missense | unknown | MSH6 A1204E lies within the ATPase domain of the Msh6 protein (PMID: 17531815). A1204E has been identified in sequencing studies (PMID: 22832583), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A1204P | missense | unknown | MSH6 A1204P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). A1204P has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A1320Sfs*5 | frameshift | unknown | MSH6 A1320Sfs*5 indicates a shift in the reading frame starting at amino acid 1320 and terminating 5 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). A1320Sfs*5 has been identified in the scientific literature (PMID: 35739269, PMID: 33393477, PMID: 18809606), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| A175T | missense | unknown | MSH6 A175T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A175T has been identified in sequencing studies (PMID: 27302833), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A175V | missense | unknown | MSH6 A175V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A175V demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| A20V | missense | unknown | MSH6 A20V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A20V demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| A25S | missense | no effect | MSH6 A25S does not lie within any known functional domains of the Msh6 protein (UniProt.org). A25S demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), and was not identified to interfere with Msh6 mismatch repair activity in a functional screen (PMID: 28531214). | |
| A297T | missense | unknown | MSH6 A297T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A297T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A322V | missense | unknown | MSH6 A322V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A322V has been identified in sequencing studies (PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A326V | missense | unknown | MSH6 A326V does not lie within any known functional domains of the Msh6 protein (PMID: 17531815). A326V demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| A339D | missense | unknown | MSH6 A339D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). A339D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A457D | missense | unknown | MSH6 A457D lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). A457D has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| A457V | missense | unknown | MSH6 A457V lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). A457V has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A587P | missense | loss of function | MSH6 A587P lies within the connector domain of the Msh6 protein (PMID: 17531815). A587P (corresponding to A586P in mouse) results in deficient mismatch repair activity in a functional screen in mouse cells, decreased Msh6 expression, increased microsatellite instability as indicated by elevated slippage rate, and increased methylation-damage-induced mutagenesis in cultured cells (PMID: 28531214). | |
| A64V | missense | unknown | MSH6 A64V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A64V has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| A81T | missense | unknown | MSH6 A81T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A81T does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| amp | none | no effect | MSH6 amplification indicates an increased number of copies of the MSH6 gene. However, the mechanism causing the increase is unspecified. | |
| C1165R | missense | loss of function - predicted | MSH6 C1165R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). C1165R (corresponds to C1163R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| C496Y | missense | unknown | MSH6 C496Y lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). C496Y demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| C615F | missense | unknown | MSH6 C615F lies within the connector domain of the Msh6 protein (PMID: 17531815). C615F has been identified in sequencing studies (PMID: 28002797), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| C694R | missense | loss of function - predicted | MSH6 C694R lies within the connector domain of the Msh6 protein (PMID: 17531815). C694R (corresponds to C691R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| C88W | missense | unknown | MSH6 C88W does not lie within any known functional domains of the Msh6 protein (UniProt.org). C88W has been identified in sequencing studies (PMID: 22941188, PMID: 26168399), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D1026Y | missense | unknown | MSH6 D1026Y lies within the lever domain of the Msh6 protein (PMID: 17531815). D1026Y demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| D1171fs | frameshift | loss of function - predicted | MSH6 D1171fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1171 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). D1171fs (reported as D1171fs*5) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| D1213E | missense | loss of function - predicted | MSH6 D1213E lies within the ATPase domain of the Msh6 protein (PMID: 17531815). D1213E (corresponds to D1211E in mouse) results in similar ATP and mismatch binding to wild-type protein, but demonstrates reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| D1213G | missense | loss of function - predicted | MSH6 D1213G lies within the ATPase domain of the Msh6 protein (PMID: 17531815). D1213G (corresponds to D1211G in mouse) results in similar ATP and mismatch binding to wild-type protein, but demonstrates reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| D197H | missense | unknown | MSH6 D197H does not lie within any known functional domains of the Msh6 protein (UniProt.org). D197H has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D358E | missense | unknown | MSH6 D358E lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D358E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D358N | missense | unknown | MSH6 D358N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D358N has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D390N | missense | unknown | MSH6 D390N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D390N has been identified in sequencing studies (PMID: 10786688), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D422G | missense | unknown | MSH6 D422G lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D422G has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D530Y | missense | unknown | MSH6 D530Y lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D530Y has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D667V | missense | unknown | MSH6 D667V lies within the connector domain of the Msh6 protein (PMID: 17531815). D667V has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| D803G | missense | loss of function - predicted | MSH6 D803G lies within the lever domain of the Msh6 protein (PMID: 17531815). D803G results in reduced affinity for ATP and decreased ATPase activity in in vitro assays (PMID: 18790734), and is therefore predicted to lead to a loss of Msh6 protein function. | |
| D89E | missense | unknown | MSH6 D89E does not lie within any known functional domains of the Msh6 protein (UniProt.org). D89E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1163V | missense | unknown | MSH6 E1163V lies within the ATPase domain of the Msh6 protein (PMID: 17531815). E1163V does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E1193K | missense | loss of function | MSH6 E1193K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). E1193K results in subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), but confers a loss of function to the Msh6 protein as indicated by decreased dimerization with Msh2 and failure to complement mismatch repair activity in Msh6-deficient cells in culture (PMID: 15354210). | |
| E1196* | nonsense | unknown | MSH6 E1196* results in a premature truncation of the Msh6 protein at amino acid 1196 of 1360 (UniProt.org). E1196* has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1214* | nonsense | unknown | MSH6 E1214* results in a premature truncation of the Msh6 protein at amino acid 1214 of 1360 (UniProt.org). E1214* has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1234* | nonsense | unknown | MSH6 E1234* results in a premature truncation of the Msh6 protein at amino acid 1234 of 1360 (UniProt.org). E1234* has been identified in the scientific literature (PMID: 27149842, PMID: 35101943, PMID: 36765365), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1254del | deletion | unknown | MSH6 E1254del results in the deletion of an amino acid in the ATPase domain of the Msh6 protein at amino acid 1254 (PMID: 17531815). E1254del has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1322* | nonsense | unknown | MSH6 E1322* results in a premature truncation of the Msh6 protein at amino acid 1322 of 1360 (UniProt.org). E1322* has been identified in the scientific literature (PMID: 36765365, PMID: 31175329, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E1322K | missense | unknown | MSH6 E1322K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). E1322K does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E171Q | missense | unknown | MSH6 E171Q does not lie within any known functional domains of the Msh6 protein (UniProt.org). E171Q does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E181A | missense | unknown | MSH6 E181A does not lie within any known functional domains of the Msh6 protein (UniProt.org). E181A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E220D | missense | unknown | MSH6 E220D does not lie within any known functional domains of the Msh6 protein (UniProt.org). E220D does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E221D | missense | unknown | MSH6 E221D does not lie within any known functional domains of the Msh6 protein (UniProt.org). E221D was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E224* | nonsense | loss of function - predicted | MSH6 E224* results in a premature truncation of the Msh6 protein at amino acid 224 of 1360 (UniProt.org). E224* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E286K | missense | unknown | MSH6 E286K does not lie within any known functional domains of the Msh6 protein (UniProt.org). E286K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E463* | nonsense | loss of function - predicted | MSH6 E463* results in a premature truncation of the Msh6 protein at amino acid 463 of 1360 (UniProt.org). E463* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E484K | missense | unknown | MSH6 E484K lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). E484K has been identified in sequencing studies (PMID: 28912153), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| E544D | missense | unknown | MSH6 E544D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). E544D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E544fs | frameshift | loss of function - predicted | MSH6 E544fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 544 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). E544fs (reported as E544fs*26) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| E597Q | missense | unknown | MSH6 E597Q lies within the connector domain of the Msh6 protein (PMID: 17531815). E597Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| E604* | nonsense | loss of function - predicted | MSH6 E604* results in a premature truncation of the Msh6 protein at amino acid 604 of 1360 (UniProt.org). E604* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E619* | nonsense | loss of function - predicted | MSH6 E619* results in a premature truncation of the Msh6 protein at amino acid 619 of 1360 (UniProt.org). E619* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E641* | nonsense | loss of function - predicted | MSH6 E641* results in a premature truncation of the Msh6 protein at amino acid 641 of 1360 (UniProt.org). E641* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E908* | nonsense | loss of function - predicted | MSH6 E908* results in a premature truncation of the Msh6 protein at amino acid 908 of 1360 (UniProt.org). E908* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E946* | nonsense | loss of function - predicted | MSH6 E946* results in a premature truncation of the Msh6 protein at amino acid 946 of 1360 (UniProt.org). E946* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| E946D | missense | unknown | MSH6 E946D lies within the clamp domain of the Msh6 protein (PMID: 17531815). E946D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| E956D | missense | unknown | MSH6 E956D lies within the clamp domain of the Msh6 protein (PMID: 17531815). E956D has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| E983Q | missense | unknown | MSH6 E983Q lies within the clamp domain of the Msh6 protein (PMID: 17531815). E983Q does not interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| E993K | missense | unknown | MSH6 E993K lies within the clamp domain of the Msh6 protein (PMID: 17531815). E993K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F1088fs | frameshift | unknown | MSH6 F1088fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1088 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). F1088fs has been identified in the scientific literature (PMID: 35237514, PMID: 32449172, PMID: 33117677), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F1088Lfs*5 | frameshift | unknown | MSH6 F1088Lfs*5 indicates a shift in the reading frame starting at amino acid 1088 and terminating 5 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). F1088Lfs*5 has been identified in the scientific literature (PMID: 30877237, PMID: 29945567, PMID: 36091175), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F1088Sfs*2 | frameshift | unknown | MSH6 F1088Sfs*2 indicates a shift in the reading frame starting at amino acid 1088 and terminating 2 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). F1088Sfs*2 has been identified in the scientific literature (PMID: 32923878, PMID: 31857677, PMID: 30877237), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| F1103L | missense | unknown | MSH6 F1103L lies within the ATPase domain of the Msh6 protein (PMID: 17531815). F1103L has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F340S | missense | unknown | MSH6 F340S lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). F340S does not demonstrate reduced mismatch repair activity compared to wild-type Msh6 in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| F432L | missense | loss of function - predicted | MSH6 F432L lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). F432L (corresponds to F431L in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| F432S | missense | loss of function - predicted | MSH6 F432S lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). F432S (corresponds to F431S in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| F573fs | frameshift | loss of function - predicted | MSH6 F573fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 573 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). F573fs has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| F689L | missense | unknown | MSH6 F689L lies within the connector domain of the Msh6 protein (PMID: 17531815). F689L has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F689V | missense | unknown | MSH6 F689V lies within the connector domain of the Msh6 protein (PMID: 17531815). F689V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| F706S | missense | loss of function - predicted | MSH6 F706S lies within the connector domain of the Msh6 protein (PMID: 17531815). F706S demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G1072C | missense | unknown | MSH6 G1072C lies within the lever domain of the Msh6 protein (PMID: 17531815). G1072C has been identified in sequencing studies (PMID: 27245685), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G1105Wfs*3 | frameshift | unknown | MSH6 G1105Wfs*3 indicates a shift in the reading frame starting at amino acid 1105 and terminating 3 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). G1105Wfs*3 has been identified in the scientific literature (PMID: 28922847, PMID: 33840814), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Mar 2024). | |
| G1139Afs*6 | frameshift | unknown | MSH6 G1139Afs*6 indicates a shift in the reading frame starting at amino acid 1139 and terminating 6 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). G1139Afs*6 has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| G1139D | missense | loss of function - predicted | MSH6 G1139D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1139D (corresponds to G1137D in mouse) results in reduced mismatch binding, impaired ATP binding, and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G1139S | missense | loss of function | MSH6 G1139S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1139S (corresponds to G1137S in mouse) results in subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), but confers a loss of function to the Msh6 protein as indicated by reduced mismatch binding and impaired ATP binding (PMID: 31965077), defective mismatch repair activity in in vitro assays (PMID: 22102614, PMID: 31965077), elevated microsatellite instability, and impaired DNA damage response in mouse cells (PMID: 24040339). | |
| G1157D | missense | loss of function - predicted | MSH6 G1157D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1157D (corresponds to G1155D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G1157S | missense | loss of function - predicted | MSH6 G1157S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1157S results in splicing similar to wild-type Msh6 but decreased mismatch repair in an in vitro assay (PMID: 32849802), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G1299C | missense | unknown | MSH6 G1299C lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1299C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G1299D | missense | unknown | MSH6 G1299D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1299D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G1316R | missense | unknown | MSH6 G1316R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1316R has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G141D | missense | unknown | MSH6 G141D lies within the PWWP domain of the Msh6 protein (UniProt.org). G141D has been identified in sequencing studies (PMID: 30545397), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| G289D | missense | unknown | MSH6 G289D does not lie within any known functional domains of the Msh6 protein (UniProt.org). G289D does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| G39E | missense | unknown | MSH6 G39E does not lie within any known functional domains of the Msh6 protein (UniProt.org). G39E is a common Msh6 polymorphism (PMID: 31552911, PMID: 24622885, PMID: 19582761), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| G39W | missense | unknown | MSH6 G39W does not lie within any known functional domains of the Msh6 protein (UniProt.org). G39W has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G467D | missense | unknown | MSH6 G467D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). G467D does not demonstrate reduced mismatch repair activity compared to wild-type Msh6 in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| G520D | missense | loss of function - predicted | MSH6 G520D lies within the connector domain of the Msh6 protein (PMID: 17531815). G520D (corresponds to G519D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G520V | missense | loss of function - predicted | MSH6 G520V lies within the connector domain of the Msh6 protein (PMID: 17531815). G520V (corresponds to G519V in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G529C | missense | unknown | MSH6 G529C lies within the connector domain of the Msh6 protein (PMID: 17531815). G529C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G557D | missense | loss of function - predicted | MSH6 G557D lies within the connector domain of the Msh6 protein (PMID: 17531815). G557D (corresponds to G556D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G566R | missense | loss of function | MSH6 G566R lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). G566R results in subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), but confers a loss of function to the Msh6 protein as indicated by deficient ATP binding and decreased Msh6 ATPase activity in in vitro assays (PMID: 18790734). | |
| G624S | missense | unknown | MSH6 G624S lies within the connector domain of the Msh6 protein (PMID: 17531815). G624S has been identified in sequencing studies (PMID: 21097718, PMID: 32095738), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| G670R | missense | unknown | MSH6 G670R lies within the connector domain of the Msh6 protein (PMID: 17531815). G670R does not interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| G686D | missense | loss of function - predicted | MSH6 G686D lies within the connector domain of the Msh6 protein (PMID: 17531815). G686D demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| G881delinsKS | indel | no effect - predicted | MSH6 G881delinsKS results in a deletion of glycine (G) at amino acid 881 within the lever domain of the Msh6 protein, combined with the insertion of a lysine (K) and a serine (S) at the same site (PMID: 17531815). G881delinsKS results in dimerization with Msh2 similar to wild-type Msh6 in cultured cells and complements mismatch repair activity in Msh6-deficient cells (PMID: 15354210), and therefore, is predicted to have no effect on Msh6 protein function. | |
| G93E | missense | unknown | MSH6 G93E lies within the PWWP domain of the Msh6 protein (UniProt.org). G93E has been identified in sequencing studies (PMID: 29245953), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| H1248D | missense | loss of function | MSH6 H1248D lies within the ATPase domain of the Msh6 protein (PMID: 18790734). H1248D results in decreased Msh6 ATPase activity and reduced affinity for mismatch DNA in in vitro assays (PMID: 18790734). | |
| H1248R | missense | unknown | MSH6 H1248R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). H1248R (corresponds to H1246R in mouse) results in similar ATP and mismatch binding to wild-type Msh6, but demonstrates intermediate mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown. | |
| H367R | missense | loss of function - predicted | MSH6 H367R lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). H367R demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| H437R | missense | loss of function - predicted | MSH6 H437R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). H437R (corresponds to H436R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| H458Y | missense | loss of function - predicted | MSH6 H458Y lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). H458Y (corresponds to H457Y in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| hypermethylation | unknown | unknown | MSH6 hypermethylation indicates an increased methylation of the MSH6 gene. However, the mechanism causing the hypermethylation is unspecified. | |
| I1054F | missense | unknown | MSH6 I1054F lies within the lever domain of the Msh6 protein (PMID: 17531815). I1054F does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| I1109fs | frameshift | loss of function - predicted | MSH6 I1109fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1109 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). I1109fs (reported as I1109fs*3) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to lead to a loss of Msh6 protein function. | |
| I1113S | missense | loss of function - predicted | MSH6 I1113S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). I1113S demonstrates impaired mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| I1183K | missense | unknown | MSH6 I1183K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). I1183K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I1183T | missense | unknown | MSH6 I1183T lies within the ATPase domain of the Msh6 protein (PMID: 17531815). I1183T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I1283fs | frameshift | unknown | MSH6 I1283fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1283 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). I1283fs has been identified in the scientific literature (PMID: 34018286), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I1357N | missense | unknown | MSH6 I1357N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). I1357N has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I258T | missense | unknown | MSH6 I258T does not lie within any known functional domains of the Msh6 protein (UniProt.org). I258T has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I425T | missense | unknown | MSH6 I425T lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). I425T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I516N | missense | loss of function - predicted | MSH6 I516N lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). I516N (corresponds to I515N in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| I516Sfs*55 | frameshift | loss of function - predicted | MSH6 I516Sfs*55 indicates a shift in the reading frame starting at amino acid 516 and terminating 55 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). I516Sfs*55 has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| I872fs | frameshift | loss of function - predicted | MSH6 I872fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 872 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). I872fs (reported as I872fs*10) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| I944V | missense | unknown | MSH6 I944V lies within the clamp domain of the Msh6 protein (PMID: 17531815). I944V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| I967K | missense | loss of function - predicted | MSH6 I967K lies within the clamp domain of the Msh6 protein (PMID: 17531815). I967K (corresponds to I964K in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| inact mut | unknown | loss of function | MSH6 inact mut indicates that this variant results in a loss of function of the Msh6 protein. However, the specific amino acid change has not been identified. | |
| K1009I | missense | unknown | MSH6 K1009I lies within the lever domain of the Msh6 protein (PMID: 17531815). K1009I has been identified in sequencing studies (PMID: 35128723), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K1013N | missense | unknown | MSH6 K1013N lies within the lever domain of the Msh2 protein (PMID: 17531815). K1013N has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K1014del | deletion | unknown | MSH6 K1014del results in the deletion of an amino acid in the lever domain of the Msh6 protein at amino acid 1014 (PMID: 17531815). K1014del has been identified in the scientific literature (PMID: 29875428, PMID: 36260514), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K1101N | missense | unknown | MSH6 K1101N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). K1101N is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K125* | nonsense | loss of function - predicted | MSH6 K125* results in a premature truncation of the Msh6 protein at amino acid 125 of 1360 (UniProt.org). K125* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| K125fs | frameshift | loss of function - predicted | MSH6 K125fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 125 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). K125fs has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| K1358Dfs*2 | frameshift | unknown | MSH6 K1358Dfs*2 indicates a shift in the reading frame starting at amino acid 1358 and terminating 2 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). K1358Dfs*2 has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| K1358fs | frameshift | unknown | MSH6 K1358fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1358 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). K1358fs has been identified in the scientific literature (PMID: 26436112, PMID: 34620004, PMID: 35958441), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K13T | missense | unknown | MSH6 K13T does not lie within any known functional domains of the Msh6 protein (UniProt.org). K13T demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K155R | missense | unknown | MSH6 K155R does not lie within any known functional domains of the Msh6 protein (UniProt.org). K155R has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| K185T | missense | unknown | MSH6 K185T does not lie within any known functional domains of the Msh6 protein (UniProt.org). K185T has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K234fs | frameshift | loss of function - predicted | MSH6 K234fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 234 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). K234fs has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| K295R | missense | unknown | MSH6 K295R does not lie within any known functional domains of the Msh6 protein (UniProt.org). K295R results in nuclear localization similar to wild-type Msh6 in cultured cells (PMID: 21437237), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K324R | missense | unknown | MSH6 K324R does not lie within any known functional domains of the Msh6 protein (UniProt.org). K324R does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K417E | missense | unknown | MSH6 K417E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). K417E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K428T | missense | unknown | MSH6 K428T lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). K428T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K431T | missense | unknown | MSH6 K431T lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). K431T has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K610N | missense | unknown | MSH6 K610N lies within the connector domain of the Msh6 protein (PMID: 17531815). K610N demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K646R | missense | unknown | MSH6 K646R lies within the connector domain of the Msh6 protein (PMID: 17531815). K646R has been identified in sequencing studies (PMID: 37007083, PMID: 32980694), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| K692N | missense | unknown | MSH6 K692N lies within the connector domain of the Msh6 protein (PMID: 17531815). K692N has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| K693fs | frameshift | loss of function - predicted | MSH6 K693fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 693 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). K693fs has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| K728T | missense | no effect - predicted | MSH6 K728T lies within the lever domain of the Msh6 protein (PMID: 17531815). K728T results in dimerization with Msh2 similar to wild-type Msh6 in cultured cells and complements mismatch repair activity in Msh6-deficient cells (PMID: 15354210), and therefore, is predicted to have no effect on Msh6 protein function. | |
| K854M | missense | unknown | MSH6 K854M lies within the lever domain of the Msh6 protein (PMID: 18790734). K854M does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| K885N | missense | unknown | MSH6 K885N lies within the lever domain of the Msh6 protein (PMID: 17531815). K885N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| K99N | missense | unknown | MSH6 K99N lies within the PWWP domain of the Msh6 protein (UniProt.org). K99N is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| L1063R | missense | loss of function - predicted | MSH6 L1063R lies within the lever domain of the Msh6 protein (PMID: 17531815). L1063R demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L1143P | missense | loss of function - predicted | MSH6 L1143P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1143P (corresponds to L1141P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L1167P | missense | loss of function - predicted | MSH6 L1167P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1167P (corresponds to L1165P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L1211P | missense | loss of function - predicted | MSH6 L1211P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1211P demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L1354Q | missense | no effect - predicted | MSH6 L1354Q lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1354Q (corresponding to L1352Q in mouse) results in Msh6 expression and Msh2 interaction similar to wild-type, proficient mismatch repair activity, suppression of microsatellite instability in cultured cells (PMID: 24040339), and subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), and therefore, is predicted to have no effect on Msh6 protein function. | |
| L290* | nonsense | loss of function - predicted | MSH6 L290* results in a premature truncation of the Msh6 protein at amino acid 290 of 1360 (UniProt.org). L290* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| L373P | missense | unknown | MSH6 L373P lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L373P has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| L396V | missense | unknown | MSH6 L396V lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L396V demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| L403I | missense | unknown | MSH6 L403I lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L403I demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| L423I | missense | unknown | MSH6 L423I lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L423I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| L435P | missense | loss of function - predicted | MSH6 L435P lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L435P results in decreased Msh6 stability in cultured cells and loss of mismatch repair activity in an in vitro assay (PMID: 22581703), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L449P | missense | loss of function - predicted | MSH6 L449P lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L449P (corresponds to L448P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L585P | missense | loss of function - predicted | MSH6 L585P lies within the connector domain of the Msh6 protein (PMID: 17531815). L585P results in decreased Msh6 stability in cultured cells and loss of mismatch repair activity in an in vitro assay (PMID: 22581703), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L634fs | frameshift | loss of function - predicted | MSH6 L634fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 634 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). L634fs has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| L637P | missense | loss of function - predicted | MSH6 L637P lies within the connector domain of the Msh6 protein (PMID: 17531815). L637P (corresponds to L636P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L681F | missense | unknown | MSH6 L681F lies within the connector domain of the Msh6 protein (PMID: 17531815). L681F has been identified in sequencing studies (PMID: 22980975, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| L773P | missense | loss of function - predicted | MSH6 L773P lies within the lever domain of the Msh6 protein (PMID: 17531815). L773P (corresponds to L770P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L821P | missense | loss of function - predicted | MSH6 L821P lies within the lever domain of the Msh6 protein (PMID: 17531815). L821P (corresponds to L818P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| L893Q | missense | unknown | MSH6 L893Q lies within the lever domain of the Msh6 protein (PMID: 17531815). L893Q has been identified in sequencing studies (PMID: 22941188), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| L979V | missense | unknown | MSH6 L979V lies within the clamp domain of the Msh6 protein (PMID: 17531815). L979V has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| loss | unknown | loss of function | MSH6 loss indicates loss of the MSH6 gene, mRNA, and protein. | |
| M1137K | missense | loss of function - predicted | MSH6 M1137K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). M1137K (corresponds to M1135K in mouse) results in impaired ATP binding, decreased mismatch binding, and reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| M1156K | missense | unknown | MSH6 M1156K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). M1156K has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| M452V | missense | unknown | MSH6 M452V lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). M452V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| M492V | missense | unknown | MSH6 M492V lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). M492V demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| M868I | missense | unknown | MSH6 M868I lies within the lever domain of the Msh6 protein (PMID: 17531815). M868I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| M868T | missense | unknown | MSH6 M868T lies within the lever domain of the Msh6 protein (PMID: 17531815). M868T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| mutant | unknown | unknown | MSH6 mutant indicates an unspecified mutation in the MSH6 gene. | |
| N1136K | missense | loss of function - predicted | MSH6 N1136K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). N1136K (corresponds to N1134K in mouse) results in mismatch binding similar to wild-type protein, however, demonstrates deficient ATP binding and mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| N897H | missense | unknown | MSH6 N897H lies within the lever domain of the Msh6 protein (PMID: 17531815). N897H has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| N960T | missense | unknown | MSH6 N960T lies within the clamp domain of the Msh6 protein (PMID: 17531815). N960T has been identified in the scientific literature (PMID: 25224212), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| negative | unknown | loss of function | MSH6 negative indicates a lack of expression of the MSH6 mRNA and/or protein. | |
| P1073S | missense | unknown | MSH6 P1073S lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). P1073S demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| P1077S | missense | unknown | MSH6 P1077S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1077S has been identified in sequencing studies (PMID: 29245953), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P1082L | missense | unknown | MSH6 P1082L lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1082L has been identified in sequencing studies (PMID: 25503501, PMID: 30603682, PMID: 29368341), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P1082S | missense | unknown | MSH6 P1082S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1082S has been identified in the scientific literature (PMID: 24100870), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| P1087R | missense | no effect | MSH6 P1087R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1087R demonstrates binding to Msh2, in vitro mismatch repair activity (PMID: 12019211, PMID: 21120944), and subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212). | |
| P1087S | missense | unknown | MSH6 P1087S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1087S demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| P1087T | missense | no effect | MSH6 P1087T lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1087T demonstrates binding to Msh2 and in vitro mismatch repair activity similar to wild-type Msh6 (PMID: 12019211, PMID: 21120944). | |
| P1097S | missense | unknown | MSH6 P1097S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1097S has been identified in sequencing studies (PMID: 28002797, PMID: 35522273), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P233S | missense | unknown | MSH6 P233S does not lie within any known functional domains of the Msh6 protein (UniProt.org). P233S has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| P591Q | missense | unknown | MSH6 P591Q lies within the connector domain of the Msh6 protein (PMID: 17531815). P591Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P623A | missense | unknown | MSH6 P623A lies within the connector domain of the Msh6 protein (PMID: 17531815). P623A was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| P623L | missense | no effect - predicted | MSH6 P623L lies within the connector domain of the Msh6 protein (PMID: 17531815). P623L results in dimerization with Msh2 similar to wild-type Msh6 in cultured cells, complements mismatch repair activity in Msh6-deficient cells (PMID: 15354210), and leads to subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), and therefore, is predicted to have no effect on Msh6 protein function. | |
| P768H | missense | unknown | MSH6 P768H lies within the lever domain of the Msh6 protein (PMID: 17531815). P768H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P781T | missense | unknown | MSH6 P781T lies within the lever domain of the Msh6 protein (PMID: 17531815). P781T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| P982A | missense | unknown | MSH6 P982A lies within the clamp domain of the Msh6 protein (PMID: 17531815). P982A has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| positive | unknown | unknown | MSH6 positive indicates the presence of the MSH6 gene, mRNA, and/or protein. | |
| Q485K | missense | unknown | MSH6 Q485K lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). Q485K (corresponds to Q484K in mouse) results in similar ATP binding to wild-type Msh6, but intermediate mismatch repair activity, and reduced mismatch binding in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown. | |
| Q485R | missense | unknown | MSH6 Q485R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). Q485R (corresponds to Q484R in mouse) results in similar ATP binding as wild-type Msh6, but intermediate mismatch repair activity, and reduced mismatch binding in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown. | |
| Q522R | missense | unknown | MSH6 Q522R lies within the connector domain of the Msh6 protein (PMID: 17531815). Q522R demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| Q618* | nonsense | loss of function - predicted | MSH6 Q618* results in a premature truncation of the Msh6 protein at amino acid 618 of 1360 (UniProt.org). Q618* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| Q698E | missense | unknown | MSH6 Q698E lies within the connector domain of the Msh6 protein (PMID: 17531815). Q698E has been identified in the scientific literature (PMID: 22290698), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| Q776H | missense | unknown | MSH6 Q776H lies within the lever domain of the Msh6 protein (PMID: 17531815). Q776H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R1024W | missense | unknown | MSH6 R1024W lies within the lever domain of the Msh6 protein (PMID: 17531815). R1024W is predicted to have a pathogenic effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| R1034Q | missense | unknown | MSH6 R1034Q lies within the lever domain of the Msh6 protein (PMID: 17531815). R1034Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R1076C | missense | unknown | MSH6 R1076C lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1076C has been identified in the scientific literature (PMID: 33422121, PMID: 22250089, PMID: 26832770), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Mar 2024). | |
| R1076H | missense | unknown | MSH6 R1076H lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1076H has been identified in sequencing studies (PMID: 29263802, PMID: 32659497), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| R1095C | missense | unknown | MSH6 R1095C lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1095C was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| R1095H | missense | no effect | MSH6 R1095H lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1095H demonstrates DNA mismatch repair activity, expression, and MSH2-interaction ability similar to wild-type Msh6 protein in cell culture (PMID: 24040339, PMID: 21120944, PMID: 12522549). | |
| R128H | missense | unknown | MSH6 R128H lies within the PWWP domain of the Msh6 protein (UniProt.org). R128H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| R128L | missense | no effect - predicted | MSH6 R128L lies within the PWWP domain of the Msh6 protein (UniProt.org). R128L results in dimerization with Msh2 similar to wild-type Msh6 in cultured cells and complements mismatch repair activity in Msh6-deficient cells (PMID: 15354210), and therefore, is predicted to have no effect on Msh6 protein function. | |
| R1304K | missense | no effect - predicted | MSH6 R1304K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1304K was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function. | |
| R1331* | nonsense | unknown | MSH6 R1331* results in a premature truncation of the Msh6 protein at amino acid 1331 of 1360 (UniProt.org). R1331* has been identified in the scientific literature (PMID: 16418736, PMID: 26552419, PMID: 32354708), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R1331P | missense | unknown | MSH6 R1331P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1331P results in subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| R1331Q | missense | unknown | MSH6 R1331Q lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1331Q has been identified in sequencing studies (PMID: 31857677), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| R1334Q | missense | loss of function | MSH6 R1334Q lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1334Q (corresponding to R1332Q in mouse) results in deficient mismatch repair activity in a functional screen in mouse cells, decreased Msh6 expression, increased microsatellite instability as indicated by elevated slippage rate, and increased methylation-damage-induced mutagenesis in cultured cells (PMID: 28531214). | |
| R1334W | missense | unknown | MSH6 R1334W lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1334W has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R178H | missense | unknown | MSH6 R178H does not lie within any known functional domains of the Msh6 protein (UniProt.org). R178H has been identified in sequencing studies (PMID: 31857677), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| R240* | nonsense | loss of function - predicted | MSH6 R240* results in a premature truncation of the Msh6 protein at amino acid 240 of 1360 (UniProt.org). R240* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| R361H | missense | unknown | MSH6 R361H lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). R361H has been identified in the scientific literature (PMID: 26674132, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R383G | missense | unknown | MSH6 R383G lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R383G has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R468H | missense | no effect - predicted | MSH6 R468H lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R468H was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function. | |
| R482Q | missense | unknown | MSH6 R482Q lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R482Q has been identified in sequencing studies (PMID: 37216304), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| R495* | nonsense | loss of function - predicted | MSH6 R495* results in a premature truncation of the Msh6 protein at amino acid 495 of 1360 (UniProt.org). R495* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| R511G | missense | loss of function - predicted | MSH6 R511G lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R511G (corresponds to V508E in mouse) demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| R577H | missense | unknown | MSH6 R577H lies within the connector domain of the Msh6 protein (PMID: 17531815). R577H is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| R644S | missense | unknown | MSH6 R644S lies within the connector domain of the Msh6 protein (PMID: 17531815). R644S is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| R761M | missense | unknown | MSH6 R761M lies within the lever domain of the Msh6 protein (PMID: 17531815). R761M has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| R772W | missense | loss of function | MSH6 R772W lies within the lever domain of the Msh6 protein (PMID: 17531815). R772W confers a loss of function to the Msh6 protein as demonstrated by impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087). | |
| R791C | missense | unknown | MSH6 R791C lies within the lever domain of the Msh6 protein (PMID: 17531815). R791C has been identified in sequencing studies (PMID: 25855536, PMID: 31391288), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2024). | |
| R791H | missense | unknown | MSH6 R791H lies within the lever domain of the Msh6 protein (PMID: 17531815). R791H has been identified in sequencing studies (PMID: 25233892, PMID: 31031019), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2024). | |
| R922* | nonsense | loss of function - predicted | MSH6 R922* results in a premature truncation of the Msh6 protein at amino acid 922 of 1360 (UniProt.org). R922* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| R922Q | missense | no effect - predicted | MSH6 R922Q lies within the lever domain of the Msh6 protein (PMID: 17531815). R922Q was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function. | |
| R959H | missense | unknown | MSH6 R959H lies within the clamp domain of the Msh6 protein (PMID: 17531815). R959H has been identified in sequencing studies (PMID: 26648449, PMID: 29596542), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2024). | |
| R961I | missense | unknown | MSH6 R961I lies within the clamp domain of the Msh6 protein (PMID: 17531815). R961I has been identified in sequencing studies (PMID: 22895193, PMID: 31391288), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2024). | |
| R976H | missense | unknown | MSH6 R976H lies within the clamp domain of the Msh6 protein (PMID: 18790734). R976H results in decreased Msh6 affinity for ADP and mismatched DNA in cell culture (PMID: 18790734), however, in another study demonstrated proficient mismatch repair activity (PMID: 22102614), and therefore, its effect on Msh6 protein function is unknown. | |
| S1028L | missense | unknown | MSH6 S1028L lies within the lever domain of the Msh6 protein (PMID: 17531815). S1028L has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S1049F | missense | unknown | MSH6 S1049F lies within the lever domain of the Msh6 protein (PMID: 17531815). S1049F is predicted to have a moderate effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S1067I | missense | unknown | MSH6 S1067I lies within the lever domain of the Msh6 protein (PMID: 17531815). S1067I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| S1188N | missense | loss of function - predicted | MSH6 S1188N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1188N demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| S1208F | missense | unknown | MSH6 S1208F lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1208F has been identified in sequencing studies (PMID: 24628946), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S1279N | missense | unknown | MSH6 S1279N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1279N has been identified in sequencing studies (PMID: 30171174), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S1329L | missense | unknown | MSH6 S1329L lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1329L does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S1340G | missense | unknown | MSH6 S1340G lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1340G does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S144I | missense | no effect | MSH6 S144I lies within the PWWP domain of the Msh6 protein (UniProt.org). S144I demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 31965077), and results in Msh2 and DNA binding (PMID: 12019211, PMID: 18484749, PMID: 21120944) and subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212). | |
| S2* | nonsense | loss of function - predicted | MSH6 S2* results in a premature truncation of the Msh6 protein at amino acid 2 of 1360 (UniProt.org). S2* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| S227I | missense | unknown | MSH6 S227I does not lie within any known functional domains of the Msh6 protein (UniProt.org). S227I results in nuclear localization similar to wild-type Msh6 in cultured cells (PMID: 21437237), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S285I | missense | unknown | MSH6 S285I does not lie within any known functional domains of the Msh6 protein (UniProt.org). S285I demonstrates mismatch stimulated ATPase activity similar to wild-type Msh6 protein in an in vitro ATPase assay (PMID: 18790734), and subcellular localization similar to wild-type in culture in one study (PMID: 22851212), but decreased nuclear localization in cultured cells in another study (PMID: 21437237), and therefore, its effect on Msh6 protein function is unknown. | |
| S314I | missense | unknown | MSH6 S314I does not lie within any known functional domains of the Msh6 protein (UniProt.org). S314I is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S315F | missense | unknown | MSH6 S315F does not lie within any known functional domains of the Msh6 protein (UniProt.org). S315F results in nuclear localization similar to wild-type Msh6 in cultured cells (PMID: 21437237), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S321* | nonsense | loss of function - predicted | MSH6 S321* results in a premature truncation of the Msh6 protein at amino acid 321 of 1360 (UniProt.org). S321* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| S341A | missense | unknown | MSH6 S341A lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). S341A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S360I | missense | unknown | MSH6 S360I lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). S360I is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| S394A | missense | unknown | MSH6 S394A lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). S394A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S41C | missense | unknown | MSH6 S41C does not lie within any known functional domains of the Msh6 protein (UniProt.org). S41C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| S503C | missense | unknown | MSH6 S503C lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). S503C (corresponding to S502C in mouse) demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), results in levels of tumor development similar to mouse models with wild-type Msh6, but leads to higher levels of serum antinuclear antibodies, decreased lifespan, increased infiltration of immune cells in the lungs, and altered somatic hypermutation in mouse models (PMID: 35708944). | |
| S580L | missense | loss of function - predicted | MSH6 S580L lies within the connector domain of the Msh6 protein (PMID: 17531815). S580L demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| S631F | missense | unknown | MSH6 S631F lies within the connector domain of the Msh6 protein (PMID: 17531815). S631F has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| S65L | missense | unknown | MSH6 S65L does not lie within any known functional domains of the Msh6 protein (UniProt.org). S65L demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S666P | missense | unknown | MSH6 S666P lies within the connector domain of the Msh6 protein (PMID: 17531815). S666P was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| S668C | missense | unknown | MSH6 S668C lies within the connector domain of the Msh6 protein (PMID: 17531815). S668C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S677I | missense | unknown | MSH6 S677I lies within the connector domain of the Msh6 protein (PMID: 17531815). S677I has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| S677T | missense | no effect - predicted | MSH6 S677T lies within the connector domain of the Msh6 protein (PMID: 17531815). S677T results in protein stability in cultured cells and mismatch repair activity in an in vitro assay similar to wild-type Msh6 (PMID: 22581703), and therefore, is predicted to have no effect on Msh6 protein function. | |
| S702* | nonsense | loss of function - predicted | MSH6 S702* results in a premature truncation of the Msh6 protein at amino acid 702 of 1360 (UniProt.org). S702* has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| S884T | missense | loss of function - predicted | MSH6 S884T lies within the lever domain of the Msh6 protein (PMID: 17531815). S884T (corresponds to S881T in mouse) results in similar ATP binding to wild-type protein, but demonstrates decreased mismatch binding and reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| S950I | missense | unknown | MSH6 S950I lies within the clamp domain of the Msh6 protein (PMID: 17531815). S950I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1008I | missense | loss of function - predicted | MSH6 T1008I lies within the clamp domain of the Msh6 protein (PMID: 17531815). T1008I (corresponds to T1005I in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| T1010A | missense | unknown | MSH6 T1010A lies within the lever domain of the Msh6 protein (PMID: 17531815). T1010A has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1085fs | frameshift | unknown | MSH6 T1085fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1085 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). T1085fs has been identified in sequencing studies (PMID: 23417712, PMID: 31069156, PMID: 35122027), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| T1142M | missense | unknown | MSH6 T1142M lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1142M was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| T1189I | missense | unknown | MSH6 T1189I lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1189I has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1205I | missense | unknown | MSH6 T1205I lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1205I has been identified in sequencing studies (PMID: 28002797), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1219D | missense | loss of function | MSH6 T1219D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1219D (corresponding to T1217D in mouse) retains the ability to recognize a DNA mismatch (PMID: 22277660, PMID: 15324697), results in protein expression, stability, subcellular localization, and Msh2 stability similar to wild-type Msh6, and mediates apoptosis in response to DNA damaging agents similar to wild-type Msh6 in cultured cells (PMID: 15324697) but results in loss of mismatch repair activity (PMID: 22277660, PMID: 15324697), acts as a dominant negative in in vitro assays (PMID: 22277660), and increases microsatellite instability in mouse cells (PMID: 15324697). | |
| T1219I | missense | loss of function | MSH6 T1219I lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1219I results in a loss of Msh6 protein function, as indicated by loss of mismatch-induced conformational changes and defective DNA mismatch repair activity in in vitro assays (PMID: 22277660, PMID: 31965077). | |
| T1225M | missense | unknown | MSH6 T1225M lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1225M demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| T1238A | missense | unknown | MSH6 T1238A lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1238A has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1247S | missense | unknown | MSH6 T1247S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1247S has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T1284M | missense | unknown | MSH6 T1284M lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1284M does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077) and leads to subcellular localization similar to wild-type Msh6 in culture (PMID: 22851212), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| T269S | missense | unknown | MSH6 T269S does not lie within any known functional domains of the Msh6 protein (UniProt.org). T269S is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T521K | missense | loss of function - predicted | MSH6 T521K lies within the connector domain of the Msh6 protein (PMID: 17531815). T521K (corresponds to T520K in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| T750P | missense | unknown | MSH6 T750P lies within the lever domain of the Msh6 protein (PMID: 17531815). T750P has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T757I | missense | unknown | MSH6 T757I lies within the lever domain of the Msh6 protein (PMID: 17531815). T757I has been identified in sequencing studies (PMID: 25078279, PMID: 22622578, PMID: 31471491), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Dec 2023). | |
| T767I | missense | loss of function - predicted | MSH6 T767I lies within the lever domain of the Msh6 protein (PMID: 17531815). T767I demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V1056M | missense | unknown | MSH6 V1056M lies within the lever domain of the Msh6 protein (PMID: 17531815). V1056M is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| V1350A | missense | unknown | MSH6 V1350A lies within the ATPase domain of the Msh6 protein (PMID: 17531815). V1350A has been identified in sequencing studies (PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| V304A | missense | unknown | MSH6 V304A does not lie within any known functional domains of the Msh6 protein (UniProt.org). V304A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| V398E | missense | loss of function - predicted | MSH6 V398E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V398E demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V424G | missense | loss of function - predicted | MSH6 V424G lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V424G (corresponds to V423G in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V450A | missense | unknown | MSH6 V450A lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V450A has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| V480E | missense | loss of function - predicted | MSH6 V480E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V480E demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V480L | missense | unknown | MSH6 V480L lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V480L has been identified in the scientific literature (PMID: 12732731), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| V508E | missense | loss of function - predicted | MSH6 V508E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V508E (corresponds to V507E in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V509A | missense | no effect - predicted | MSH6 V509A lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V509A was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function. | |
| V509E | missense | loss of function - predicted | MSH6 V509E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V509E (corresponds to V508E in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V688D | missense | loss of function - predicted | MSH6 V688D lies within the connector domain of the Msh6 protein (PMID: 17531815). V688D (corresponds to V685D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| V800L | missense | unknown | MSH6 V800L lies within the lever domain of the Msh6 protein (PMID: 17531815). V800L does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. | |
| V878A | missense | unknown | MSH6 V878A lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). The functional effect of V878A is conflicting, as it demonstrates decreased Msh6 ATPase activity in vitro in one study (PMID: 18790734), but demonstrates proficient mismatch repair activity in an in vitro assay in another study (PMID: 22102614), and therefore, its effect on Msh6 protein function is unknown. | |
| W1047* | nonsense | loss of function - predicted | MSH6 W1047* results in a premature truncation of the Msh6 protein at amino acid 1047 of 1360 (UniProt.org). W1047* has not been characterized, however, due to loss of the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| W142* | nonsense | loss of function - predicted | MSH6 W142* results in a premature truncation of the Msh6 protein at amino acid 142 of 1360 (UniProt.org). W142* has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to result in a loss of Msh6 protein function. | |
| W372R | missense | loss of function - predicted | MSH6 W372R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). W372R (corresponds to W371R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| W413R | missense | loss of function - predicted | MSH6 W413R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). W413R (corresponds to W412R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| W628* | nonsense | loss of function - predicted | MSH6 W628* results in a premature truncation of the Msh6 protein at amino acid 628 of 1360 (UniProt.org). W628* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| W777* | nonsense | loss of function - predicted | MSH6 W777* results in a premature truncation of the Msh6 protein at amino acid 777 of 1360 (UniProt.org). W777* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| W912R | missense | unknown | MSH6 W912R lies within the lever domain of the Msh6 protein (PMID: 17531815). W912R has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| Y1006* | nonsense | loss of function - predicted | MSH6 Y1006* results in a premature truncation of the Msh6 protein at amino acid 1006 of 1360 (UniProt.org). Y1006* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| Y1006N | missense | loss of function - predicted | MSH6 Y1006N lies within the clamp domain of the Msh6 protein (PMID: 17531815). Y1006N (corresponds to Y1003N in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| Y1044* | nonsense | loss of function - predicted | MSH6 Y1044* results in a premature truncation of the Msh6 protein at amino acid 1044 of 1360 (UniProt.org). Y1044* has not been characterized, however, due to loss of the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| Y1066Wfs*21 | frameshift | loss of function - predicted | MSH6 Y1066Wfs*21 indicates a shift in the reading frame starting at amino acid 1066 and terminating 21 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). Y1066Wfs*21 has not been characterized, however, due to loss of the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| Y1256* | nonsense | unknown | MSH6 Y1256* results in a premature truncation of the Msh6 protein at amino acid 1256 of 1360 (UniProt.org). Y1256* has been identified in the scientific literature (PMID: 35739269, PMID: 33393477, PMID: 26552419), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Nov 2023). | |
| Y397fs | frameshift | loss of function - predicted | MSH6 Y397fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 397 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). Y397fs (reported as Y397fs*3) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and therefore, is predicted to lead to a loss of Msh6 protein function. | |
| Y397H | missense | unknown | MSH6 Y397H lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). Y397H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Oct 2023). | |
| Y556F | missense | no effect - predicted | MSH6 Y556F lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). Y556F was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function. | |
| Y850* | nonsense | loss of function - predicted | MSH6 Y850* results in a premature truncation of the Msh6 protein at amino acid 850 of 1360 (UniProt.org). Y850* has not been characterized, however, due to the loss of several functional domains including the ATPase domain (PMID: 17531815, PMID: 23391514), is predicted to lead to a loss of Msh6 protein function. | |
| Y850C | missense | unknown | MSH6 Y850C lies within the lever domain of the Msh6 protein (PMID: 17531815). Y850C demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown. |
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