ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1171G>A (p.Ala391Thr) (rs878853798)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227304 SCV000284094 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 391 of the MSH2 protein (p.Ala391Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 237359). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000566323 SCV000662314 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing Insufficient evidence
Counsyl RCV000662565 SCV000785167 uncertain significance Lynch syndrome I 2017-05-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780444 SCV000917696 uncertain significance not specified 2018-05-07 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1171G>A (p.Ala391Thr) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, core domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246254 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1171G>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000566323 SCV001356423 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-24 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.