NM_005591.4(MRE11):c.140C>T (p.Ala47Val) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [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]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001171711Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Feb 15, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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]

Hypergonadotropic hypogonadism and hypersegmented neutrophils in a patient with ataxia-telangiectasia-like disorder: potential diagnostic clues?

Yoshida T, Awaya T, Shibata M, Kato T, Numabe H, Kobayashi J, Komatsu K, Heike T.

Am J Med Genet A. 2014 Jul;164A(7):1830-4. doi: 10.1002/ajmg.a.36546. Epub 2014 Apr 14.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV001171711.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)


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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Aug 3, 2021

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