ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3293G>T (p.Cys1098Phe)

gnomAD frequency: 0.00001  dbSNP: rs876660564
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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 RCV000569493 SCV000673963 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-18 criteria provided, single submitter clinical testing The p.C1098F variant (also known as c.3293G>T), located in coding exon 5 of the MSH6 gene, results from a G to T substitution at nucleotide position 3293. The cysteine at codon 1098 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. In addition, the CoDP in silico tool predicts this alteration is likely to impair molecular function, with a score of 0.998 (Terui H et al. J. Biomed. Sci. 2013;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000569493 SCV004357711 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces cytosine with phenylalanine at codon 1098 of the MSH6 gene. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 been identified in 1/31404 chromosomes 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.
All of Us Research Program, National Institutes of Health RCV004806488 SCV005429403 uncertain significance Lynch syndrome 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces cytosine with phenylalanine at codon 1098 of the MSH6 gene. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 been identified in 1/31404 chromosomes 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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