ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.541G>A (p.Glu181Lys)

gnomAD frequency: 0.00002  dbSNP: rs569728764
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001024076 SCV001186032 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-16 criteria provided, single submitter clinical testing The p.E181K variant (also known as c.541G>A), located in coding exon 3 of the MSH6 gene, results from a G to A substitution at nucleotide position 541. The glutamic acid at codon 181 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all 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.
All of Us Research Program, National Institutes of Health RCV004004645 SCV004832683 uncertain significance Lynch syndrome 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 181 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 5/251444 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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