ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2409C>G (p.Asp803Glu)

gnomAD frequency: 0.00001  dbSNP: rs1434270332
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000547711 SCV000624757 likely benign Hereditary nonpolyposis colorectal neoplasms 2022-12-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015434 SCV001176266 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-01 criteria provided, single submitter clinical testing The p.D803E variant (also known as c.2409C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 2409. The aspartic acid at codon 803 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002282203 SCV002571590 uncertain significance not provided 2024-01-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944)
All of Us Research Program, National Institutes of Health RCV004806398 SCV005429335 uncertain significance Lynch syndrome 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 803 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 MSH6-related disorders in the literature. This variant has been identified in 1/31396 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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