ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2752C>T (p.His918Tyr)

dbSNP: rs1558666591
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000708882 SCV000837904 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000734437 SCV000862581 uncertain significance not provided 2018-07-27 criteria provided, single submitter clinical testing
Mendelics RCV000986726 SCV001135825 uncertain significance Lynch syndrome 5 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001016502 SCV001177462 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-03 criteria provided, single submitter clinical testing The p.H918Y variant (also known as c.2752C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 2752. The histidine at codon 918 is replaced by tyrosine, an amino acid with similar properties. This alteration was detected in one of 1893 women with epithelial ovarian cancer from three population-based studies who were ascertained for mutations in MLH1, MSH2 and MSH6 (Pal T et al. Br J Cancer, 2012 Nov;107:1783-90). 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.
Invitae RCV001047029 SCV001210961 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 918 of the MSH6 protein (p.His918Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer, breast cancer (PMID: 23047549, 35264596, 35449176). ClinVar contains an entry for this variant (Variation ID: 584621). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MSH6 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001016502 SCV001734515 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-11 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 918 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with ovarian cancer (PMID: 23047549). This variant has not been identified 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000986726 SCV002512749 uncertain significance Lynch syndrome 5 2021-07-13 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderate
Sema4, Sema4 RCV001016502 SCV002535765 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-24 criteria provided, single submitter curation

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.