ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3674C>A (p.Thr1225Lys)

dbSNP: rs63750370
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000791493 SCV000930745 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-03-29 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MSH6 protein function. ClinVar contains an entry for this variant (Variation ID: 638837). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is present in population databases (rs63750370, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1225 of the MSH6 protein (p.Thr1225Lys).
Ambry Genetics RCV002458409 SCV002615741 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-05 criteria provided, single submitter clinical testing The p.T1225K variant (also known as c.3674C>A), located in coding exon 8 of the MSH6 gene, results from a C to A substitution at nucleotide position 3674. The threonine at codon 1225 is replaced by lysine, an amino acid with 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.
All of Us Research Program, National Institutes of Health RCV004001554 SCV004835110 uncertain significance Lynch syndrome 2023-03-28 criteria provided, single submitter clinical testing

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