ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1455G>T (p.Gln485His)

dbSNP: rs1669333625
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001230229 SCV001402703 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-08 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 485 of the MSH6 protein (p.Gln485His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine.
All of Us Research Program, National Institutes of Health RCV004004833 SCV004831484 uncertain significance Lynch syndrome 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 485 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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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