ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.146C>T (p.Ala49Val)

dbSNP: rs775498550
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233115 SCV000283715 benign Hereditary nonpolyposis colorectal neoplasms 2023-11-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000773125 SCV000906619 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-01 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 49 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 4/204472 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.
Ambry Genetics RCV000773125 SCV001172113 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-29 criteria provided, single submitter clinical testing The p.A49V variant (also known as c.146C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 146. The alanine at codon 49 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003320618 SCV004024781 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998708 SCV004828041 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 49 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 4/204472 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.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004696887 SCV005199191 uncertain significance not provided 2022-05-27 criteria provided, single submitter clinical testing

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