ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1163A>C (p.His388Pro)

dbSNP: rs786201185
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163036 SCV000213525 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-20 criteria provided, single submitter clinical testing The p.H388P variant (also known as c.1163A>C), located in coding exon 4 of the MSH6 gene, results from an A to C substitution at nucleotide position 1163. The histidine at codon 388 is replaced by proline, an amino acid with similar properties. This amino acid position is not 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002228557 SCV000551147 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-09-20 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with proline at codon 388 of the MSH6 protein (p.His388Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline.
All of Us Research Program, National Institutes of Health RCV003995225 SCV004826577 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces histidine with proline at codon 388 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders 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.

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