ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3595A>T (p.Ser1199Cys)

dbSNP: rs1558390771
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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 RCV001049722 SCV001213789 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-08-22 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: 846423). 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 serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1199 of the MSH6 protein (p.Ser1199Cys).
Ambry Genetics RCV002451202 SCV002614904 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-02 criteria provided, single submitter clinical testing The p.S1199C variant (also known as c.3595A>T), located in coding exon 7 of the MSH6 gene, results from an A to T substitution at nucleotide position 3595. The serine at codon 1199 is replaced by cysteine, an amino acid with dissimilar 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 RCV003462544 SCV004195731 uncertain significance Endometrial carcinoma 2023-06-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004795 SCV004826228 uncertain significance Lynch syndrome 2023-05-31 criteria provided, single submitter clinical testing

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