ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.649G>T (p.Asp217Tyr)

gnomAD frequency: 0.00001  dbSNP: rs950036621
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025338 SCV001187510 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-18 criteria provided, single submitter clinical testing The p.D217Y variant (also known as c.649G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 649. The aspartic acid at codon 217 is replaced by tyrosine, an amino acid with highly dissimilar properties. This alteration [also designated as c.648_649delAGinsTT if in cis with the MSH6 c.648A>T (p.T216T)] has been reported in a Portuguese patient with rectal cancer at age 45 years and was not observed in 108 control samples (Pinto C et al. Br. J. Cancer 2006 Sep;95:752-6). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004004660 SCV004836741 uncertain significance Lynch syndrome 2023-05-15 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with tyrosine at codon 217 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with an early-onset colorectal cancer (PMID: 16940983). This variant has been identified in 3/247652 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.

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.