ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.529G>A (p.Ala177Thr) (rs142996063)

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
GeneDx RCV000656867 SCV000149828 uncertain significance not provided 2013-12-24 criteria provided, single submitter clinical testing This variant is denoted MRE11A c.529G>A at the cDNA level, p.Ala177Thr (A177T) at the protein level, and results in the change of an Alanine to a Threonine (GCG>ACG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MRE11A Ala177Thr was not observed at significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a non-conservative substitution in which a neutral non-polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on the currently available information, we consider MRE11A Ala177Thr to be a variant of uncertain significance.
Ambry Genetics RCV000115919 SCV000183953 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000791435 SCV000254867 uncertain significance Ataxia-telangiectasia-like disorder 2018-11-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 177 of the MRE11 protein (p.Ala177Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs142996063, ExAC 0.03%). This variant has been reported in three individuals: two triple-negative breast cancer patients (PMID: 25452441) and one individual who was either affected with disease or had a strong family history of breast or ovarian cancer (PMID: 24549055). This variant has also been reported in a family affected with breast cancer, however, segregation data for this family is not available (PMID: 26534844). ClinVar contains an entry for this variant (Variation ID: 127983). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. 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.
Illumina Clinical Services Laboratory,Illumina RCV000400887 SCV000374941 uncertain significance Ataxia-telangiectasia-like disorder 1 2016-06-14 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000212559 SCV000614126 uncertain significance not specified 2017-01-27 criteria provided, single submitter clinical testing
Counsyl RCV000400887 SCV000785465 uncertain significance Ataxia-telangiectasia-like disorder 1 2017-08-15 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115919 SCV000822037 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000400887 SCV000894682 uncertain significance Ataxia-telangiectasia-like disorder 1 2018-10-31 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.