ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.818G>T (p.Gly273Val)

dbSNP: rs769610487
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232347 SCV000283858 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561246 SCV000669949 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-20 criteria provided, single submitter clinical testing The p.G273V variant (also known as c.818G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 818. The glycine at codon 273 is replaced by valine, an amino acid with dissimilar properties. This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated high microsatellite instability and normal mismatch repair expression by immunohistochemistry (Yang RK et al. Cancers (Basel), 2022 Sep;14). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000561246 SCV000685521 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-18 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 273 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 hereditary cancer in the literature. This variant has been identified in 1/251030 chromosomes 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.
Mendelics RCV003491994 SCV001135795 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000561246 SCV002536355 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-04 criteria provided, single submitter curation
GeneDx RCV003233509 SCV003930940 uncertain significance not provided 2023-06-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with endometrial carcinoma, which showed high microsatellite instability and proficient mismatch repair ability (Yang et al., 2022); This variant is associated with the following publications: (PMID: 33827469, 36230473)
Baylor Genetics RCV003463644 SCV004195562 uncertain significance Endometrial carcinoma 2023-08-24 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998733 SCV004837085 uncertain significance Lynch syndrome 2023-05-31 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 273 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 hereditary cancer in the literature. This variant has been identified in 1/251030 chromosomes 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000582421 SCV000691921 uncertain significance not specified no assertion criteria provided clinical testing

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