ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.476C>T (p.Ala159Val)

gnomAD frequency: 0.00002  dbSNP: rs587778528
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215694 SCV000275393 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-12 criteria provided, single submitter clinical testing The p.A159V variant (also known as c.476C>T), located in coding exon 3 of the MSH6 gene, results from a C to T substitution at nucleotide position 476. The alanine at codon 159 is replaced by valine, an amino acid with similar properties. This amino acid position is 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.
Invitae RCV000457237 SCV000551076 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586380 SCV000695915 uncertain significance not provided 2016-05-03 criteria provided, single submitter clinical testing Variant summary: The c.476C>T variant affects a conserved nucleotide, resulting in amino acid change from Ala to Val. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is found in 4/120712 control chromosomes at a frequency of 0.0000331, which does not exceed maximal expected frequency of a pathogenic allele (0.0001421). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Diagnostics, LLC DBA Color Health RCV000215694 SCV000911113 likely benign Hereditary cancer-predisposing syndrome 2017-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000586380 SCV003923353 uncertain significance not provided 2023-05-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in unaffected individuals under the age of 50 undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 23621914, 24728327)
Baylor Genetics RCV003460854 SCV004195545 uncertain significance Endometrial carcinoma 2023-08-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997351 SCV004829264 likely benign Lynch syndrome 2023-12-01 criteria provided, single submitter clinical testing
ITMI RCV000121571 SCV000085767 not provided not specified 2013-09-19 no assertion provided reference population

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