ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.533G>T (p.Arg178Leu)

gnomAD frequency: 0.00001  dbSNP: rs786204186
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570685 SCV000670054 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-22 criteria provided, single submitter clinical testing The p.R178L variant (also known as c.533G>T), located in coding exon 3 of the MSH6 gene, results from a G to T substitution at nucleotide position 533. The arginine at codon 178 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001070096 SCV001235307 benign Hereditary nonpolyposis colorectal neoplasms 2023-04-17 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000570685 SCV001359086 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 178 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 hereditary cancer in the literature. This variant has been identified in 2/251448 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844201 SCV002103393 uncertain significance not specified 2022-02-16 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000570685 SCV002536327 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-27 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004001062 SCV004841049 uncertain significance Lynch syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 178 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 hereditary cancer in the literature. This variant has been identified in 2/251448 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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