ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1618C>G (p.Leu540Val)

dbSNP: rs201996928
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160667 SCV000211277 uncertain significance not provided 2024-09-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates 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: 27923066, 17531815, 21120944)
Labcorp Genetics (formerly Invitae), Labcorp RCV000468959 SCV000551132 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491381 SCV000580234 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-06 criteria provided, single submitter clinical testing The p.L540V variant (also known as c.1618C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 1618. The leucine at codon 540 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV000491381 SCV002052030 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-02 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 540 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 hereditary cancer in the literature. This variant has been identified in 2/251312 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 RCV004806119 SCV005429282 uncertain significance Lynch syndrome 2024-07-10 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 540 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 hereditary cancer in the literature. This variant has been identified in 2/251312 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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