ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.169C>T (p.Pro57Ser)

dbSNP: rs773367009
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001207892 SCV001379260 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-10-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 57 of the MSH6 protein (p.Pro57Ser). 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: 938631). 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. 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.
All of Us Research Program, National Institutes of Health RCV004010663 SCV004830392 uncertain significance Lynch syndrome 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 57 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 not been identified 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.
Ambry Genetics RCV004033711 SCV005032690 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-28 criteria provided, single submitter clinical testing The p.P57S variant (also known as c.169C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 169. The proline at codon 57 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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