ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.140C>T (p.Ala47Val) (rs730880378)

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
Invitae RCV000157663 SCV000642119 uncertain significance Ataxia-telangiectasia-like disorder 1 2017-03-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 47 of the MRE11 protein (p.Ala47Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (rs730880378, ExAC no frequency). This variant has been reported as homozygous in an individual (from consanguineous parents) affected with progressive myoclonic ataxia (PMID: 24332946). It was also observed as heterozygous in an individual affected with ataxia-telangiectasia-like disorder, although a second MRE11 variant was not identified (PMID: 24733832). ClinVar contains an entry for this variant (Variation ID: 180713). Experimental studies have shown that this missense change reduces MRE11 protein expression, and disturbs the MRE11/RAD50/NBN (MRN) complex (PMID: 24332946, 2433832). In summary, this variant is a rare missense change that has been shown to disrupt protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001011397 SCV001171711 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-15 criteria provided, single submitter clinical testing The p.A47V variant (also known as c.140C>T), located in coding exon 2 of the MRE11A gene, results from a C to T substitution at nucleotide position 140. The alanine at codon 47 is replaced by valine, an amino acid with similar properties. This variant was reported in the homozygous state in a Japanese patient with progressive myoclonic ataxia, who underwent exome sequencing (Miyamoto R et al. J. Neurol. Sci. 2014 Feb;337:219-23). It has also been reported in the heterozygous state, in a Japanese patient with Ataxia-Telangiectasia-like disorder; this patient was not found to have another MRE11A variant (Yoshida T et al. Am. J. Med. Genet. A. 2014 Jul;164A:1830-4). Both of these patients showed reduced MRE11 protein expression compared to healthy controls (Miyamoto R et al. J. Neurol. Sci. 2014 Feb;337:219-23; Yoshida T et al. Am. J. Med. Genet. A. 2014 Jul;164A:1830-4). This alteration has also been reported in 1/235 Korean patients with Hereditary Breast Cancer, who previously tested negative for BRCA1/2 (Kim H et al. Breast Cancer Res. Treat. 2017 01;161:95-102). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
OMIM RCV000157663 SCV000207624 pathogenic Ataxia-telangiectasia-like disorder 1 2014-02-15 no assertion criteria provided literature only

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.