ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.677C>T (p.Thr226Ile)

dbSNP: rs201276188
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
Invitae RCV001361779 SCV001557769 uncertain significance Ataxia-telangiectasia-like disorder 2016-08-15 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs201276188, ExAC <0.01%) but has not been reported in the literature in individuals with a MRE11A-related disease. This sequence change replaces threonine with isoleucine at codon 226 of the MRE11A protein (p.Thr226Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine.
Ambry Genetics RCV000466940 SCV002755911 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-24 criteria provided, single submitter clinical testing The p.T226I variant (also known as c.677C>T), located in coding exon 7 of the MRE11A gene, results from a C to T substitution at nucleotide position 677. The threonine at codon 226 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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 p.T226I remains unclear.

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.