ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3620A>G (p.His1207Arg)

dbSNP: rs2104525263
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001920203 SCV002162557 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-09-01 criteria provided, single submitter clinical testing 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 C0"). 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. ClinVar contains an entry for this variant (Variation ID: 1397388). 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 histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1207 of the MSH6 protein (p.His1207Arg).
Ambry Genetics RCV002458751 SCV002615833 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-19 criteria provided, single submitter clinical testing The p.H1207R variant (also known as c.3620A>G), located in coding exon 7 of the MSH6 gene, results from an A to G substitution at nucleotide position 3620. The histidine at codon 1207 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003464212 SCV004195584 uncertain significance Endometrial carcinoma 2023-08-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010808 SCV004840047 uncertain significance Lynch syndrome 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 1207 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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