ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2080T>C (p.Cys694Arg)

dbSNP: rs587779228
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822642 SCV000963452 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-04-02 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 694 of the MSH6 protein (p.Cys694Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 21520333; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 89248). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MSH6 protein function. Experimental studies have shown that this missense change affects MSH6 function (PMID: 31965077). 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. RCV003450940 SCV004185560 likely pathogenic Lynch syndrome 5 2023-08-16 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 31965077]. This variant is expected to disrupt protein structure [Myriad internal data].
Color Diagnostics, LLC DBA Color Health RCV001186406 SCV001352808 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-10 flagged submission clinical testing

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