ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.655A>G (p.Ser219Gly)

dbSNP: rs2104289193
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Sema4, Sema4 RCV002257128 SCV002536341 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-28 criteria provided, single submitter curation
Ambry Genetics RCV002257128 SCV002665874 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-16 criteria provided, single submitter clinical testing The p.S219G variant (also known as c.655A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 655. The serine at codon 219 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005095883 SCV005731473 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 219 of the MSH6 protein (p.Ser219Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1692268). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MSH6 protein function with a negative predictive value of 95%. 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.

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