ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3843G>T (p.Glu1281Asp)

dbSNP: rs864622384
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000205009 SCV000260396 benign Hereditary nonpolyposis colorectal neoplasms 2024-04-25 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000773068 SCV000906490 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 1281 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 MSH6-related disorders in the literature. This variant has been identified in 1/250888 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 RCV000780468 SCV000917741 uncertain significance not specified 2017-11-24 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.3843G>T (p.Glu1281Asp) variant located in the DNA mismatch repair MutS, C-terminal domain (InterPro) involves the alteration of a conserved nucleotide and 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 1/245854 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421). In addition, a clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Ambry Genetics RCV000773068 SCV002623592 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-08 criteria provided, single submitter clinical testing The p.E1281D variant (also known as c.3843G>T), located in coding exon 9 of the MSH6 gene, results from a G to T substitution at nucleotide position 3843. The glutamic acid at codon 1281 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003314577 SCV004014207 uncertain significance not provided 2023-07-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944)
Baylor Genetics RCV003462376 SCV004195726 uncertain significance Endometrial carcinoma 2023-06-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005031776 SCV005658601 uncertain significance Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 2024-06-10 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.