ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2245G>A (p.Glu749Lys) (rs63751477)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076444 SCV000107472 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Abrogated function & 2 MSI-H tumours
Ambry Genetics RCV000218283 SCV000274701 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-05 criteria provided, single submitter clinical testing Deficient protein function in appropriate functional assay(s);Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other data supporting pathogenic classification;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV001062435 SCV001227235 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 749 of the MSH2 protein (p.Glu749Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 21120944, 12624141, 15849733, 21642682). ClinVar contains an entry for this variant (Variation ID: 90942). This variant has been reported to affect MSH2 protein function (PMID: 23690608, 21120944, 18470917, 18951462, 17101317). 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.

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.