ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.140C>T (p.Ala47Val) (rs730880378)

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Total submissions: 2
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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.
OMIM RCV000157663 SCV000207624 pathogenic Ataxia-telangiectasia-like disorder 1 2014-02-15 no assertion criteria provided literature only

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