ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1457C>T (p.Thr486Ile)

gnomAD frequency: 0.00001  dbSNP: rs577713548
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799965 SCV000939659 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-09-26 criteria provided, single submitter clinical testing 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: 645807). 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. 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. This variant is present in population databases (rs577713548, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 486 of the MSH6 protein (p.Thr486Ile).
Ambry Genetics RCV002388470 SCV002701915 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-22 criteria provided, single submitter clinical testing The p.T486I variant (also known as c.1457C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 1457. The threonine at codon 486 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is 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.
All of Us Research Program, National Institutes of Health RCV004001631 SCV004822746 uncertain significance Lynch syndrome 2023-06-15 criteria provided, single submitter clinical testing

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