ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.1727G>A (p.Arg576Gln) (rs139461096)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656868 SCV000149818 uncertain significance not provided 2018-09-12 criteria provided, single submitter clinical testing MRE11A has only only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted MRE11A c.1727G>A at the cDNA level, p.Arg576Gln (R576Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MRE11A Arg576Gln was observed with allele frequencies of 0.05% (4/8596) and 0.02% (1/4402) in European and African Americans in the NHLBI Exome Sequencing Project respectively, which is not frequent enough to be considered a polymorphism. This variant is a semi-conservative substitution in which a positive polar amino acid is replaced with a neutral polar one, altering a position that is moderately conserved throughout evolution and tolerates the Arg>Gln substitution. MRE11A Arg576Gln is located within the GAR (glycine-arginine-rich) motif in the DNA-binding region (Stracker 2011). Studies in mice and cell based models demonstrate the requirement for the MRE11A GAR motif in regulating the ATR activation during DNA damage signaling and the maintenance of genomic stability (Yu 2012). In silico analyses predict this variant to have a benign effect on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the MRE11A gene, remain unclear.
Ambry Genetics RCV000115909 SCV000172853 likely benign Hereditary cancer-predisposing syndrome 2017-11-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign) ,Other data supporting benign classification
Invitae RCV000656868 SCV000254857 likely benign not provided 2019-02-07 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000656868 SCV000614122 uncertain significance not provided 2017-12-22 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626883 SCV000747586 uncertain significance Dystonia; Depressivity; Parkinsonism; Dementia 2017-01-01 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115909 SCV000822029 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 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.