ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1013G>C (p.Gly338Ala)

dbSNP: rs587779065
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000663023 SCV000786044 uncertain significance Lynch syndrome 1 2018-02-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001320681 SCV001511476 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-03-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 338 of the MSH2 protein (p.Gly338Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 220628). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) did not meet the statistical confidence thresholds required to predict the impact of this variant on MSH2 function. This variant disrupts the p.Gly338 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16736289, 17720936, 23612316). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Myriad Genetics, Inc. RCV000663023 SCV004018278 uncertain significance Lynch syndrome 1 2023-03-17 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000663023 SCV005053533 uncertain significance Lynch syndrome 1 2023-11-27 criteria provided, single submitter clinical testing

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