ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3824G>C (p.Cys1275Ser)

dbSNP: rs150990541
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001243087 SCV001416221 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-07-06 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function. ClinVar contains an entry for this variant (Variation ID: 968040). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1275 of the MSH6 protein (p.Cys1275Ser).
All of Us Research Program, National Institutes of Health RCV004004895 SCV004830418 uncertain significance Lynch syndrome 2023-09-04 criteria provided, single submitter clinical testing This missense variant replaces cysteine with serine at codon 1275 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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