ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2168G>C (p.Gly723Ala)

gnomAD frequency: 0.00002  dbSNP: rs759403696
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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 RCV000166842 SCV000217656 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-13 criteria provided, single submitter clinical testing The p.G723A variant (also known as c.2168G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 2168. The glycine at codon 723 is replaced by alanine, an amino acid with 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001041140 SCV001204740 benign Hereditary nonpolyposis colorectal neoplasms 2024-11-21 criteria provided, single submitter clinical testing
GeneDx RCV001552358 SCV001773030 uncertain significance not provided 2019-09-03 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously reported as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001797654 SCV002041502 uncertain significance not specified 2021-11-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003995537 SCV004834972 uncertain significance Lynch syndrome 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 723 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 4/250920 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.
Baylor Genetics RCV004567315 SCV005054876 uncertain significance Endometrial carcinoma 2024-03-04 criteria provided, single submitter clinical testing

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