NM_005591.4(MRE11):c.140C>T (p.Ala47Val) AND Ataxia-telangiectasia-like disorder 1

Clinical significance:Uncertain significance (Last evaluated: Mar 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_005591.4(MRE11):c.140C>T (p.Ala47Val)]

NM_005591.4(MRE11):c.140C>T (p.Ala47Val)

MRE11:MRE11 homolog, double strand break repair nuclease [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_005591.4(MRE11):c.140C>T (p.Ala47Val)
  • NC_000011.10:g.94490846G>A
  • NG_007261.1:g.8029C>T
  • NM_001330347.2:c.140C>T
  • NM_005590.4:c.140C>T
  • NM_005591.3:c.140C>T
  • NM_005591.4:c.140C>TMANE SELECT
  • NP_001317276.1:p.Ala47Val
  • NP_005581.2:p.Ala47Val
  • NP_005582.1:p.Ala47Val
  • NP_005582.1:p.Ala47Val
  • LRG_85t1:c.140C>T
  • LRG_85:g.8029C>T
  • LRG_85p1:p.Ala47Val
  • NC_000011.9:g.94224012G>A
Protein change:
OMIM: 600814.0006; dbSNP: rs730880378
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001330347.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005590.4:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005591.3:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005591.4:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]


Ataxia-telangiectasia-like disorder 1 (ATLD1)
MONDO: MONDO:0024557; MedGen: C4012790; Orphanet: 251347; OMIM: 604391

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000207624OMIMno assertion criteria providedPathogenic
(Feb 15, 2014)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000642119Invitaecriteria provided, single submitter
Uncertain significance
(Mar 23, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia.

Miyamoto R, Morino H, Yoshizawa A, Miyazaki Y, Maruyama H, Murakami N, Fukada K, Izumi Y, Matsuura S, Kaji R, Kawakami H.

J Neurol Sci. 2014 Feb 15;337(1-2):219-23. doi: 10.1016/j.jns.2013.11.032. Epub 2013 Dec 1.

PubMed [citation]

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From OMIM, SCV000207624.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In a 52-year-old Japanese woman, born of consanguineous parents, with ataxia-telangiectasia-like disorder-1 (ATLD1; 604391), Miyamoto et al. (2014) identified a homozygous c.140C-T transition in the MRE11A gene, resulting in an ala47-to-val (A47V) substitution in the highly conserved nuclease domain. The mutation, which was found by a combination of linkage analysis and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Sequencing Project databases, and was not found in 174 control individuals. Western blot analysis of patient cells showed mildly decreased levels of MRE11A, RAD50 (604040), and NBS1 (NBN; 602667) that likely did not fully disrupt the MRN complex. The patient had a relatively mild disease course: she presented with subcortical myoclonus at age 9 years, and developed ataxia in her forties. Brain imaging did not show cerebellar atrophy.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000642119.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)


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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 3, 2021

Support Center