NM_000251.3(MSH2):c.2801C>A (p.Thr934Lys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Nov 21, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000564878.3

Allele description [Variation Report for NM_000251.3(MSH2):c.2801C>A (p.Thr934Lys)]

NM_000251.3(MSH2):c.2801C>A (p.Thr934Lys)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.2801C>A (p.Thr934Lys)
HGVS:
  • NC_000002.12:g.47482945C>A
  • NG_007110.2:g.84822C>A
  • NM_000251.2:c.2801C>A
  • NM_000251.3:c.2801C>AMANE SELECT
  • NM_001258281.1:c.2603C>A
  • NP_000242.1:p.Thr934Lys
  • NP_000242.1:p.Thr934Lys
  • NP_001245210.1:p.Thr868Lys
  • LRG_218t1:c.2801C>A
  • LRG_218:g.84822C>A
  • LRG_218p1:p.Thr934Lys
  • NC_000002.11:g.47710084C>A
  • NM_000251.1:c.2801C>A
Protein change:
T868K
Links:
dbSNP: rs587779969
NCBI 1000 Genomes Browser:
rs587779969
Molecular consequence:
  • NM_000251.2:c.2801C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000251.3:c.2801C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.2603C>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000673905Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Nov 21, 2018)
germlineclinical testing

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

Citation Link,

SCV001352317Color Health, Inccriteria provided, single submitter
Likely benign
(Jun 17, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA.

Br J Cancer. 2012 Nov 6;107(10):1783-90. doi: 10.1038/bjc.2012.452. Epub 2012 Oct 9.

PubMed [citation]
PMID:
23047549
PMCID:
PMC3493867

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000673905.3

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

Description

The p.T934K variant (also known as c.2801C>A), located in coding exon 16 of the MSH2 gene, results from a C to A substitution at nucleotide position 2801. The threonine at codon 934 is replaced by lysine, an amino acid with similar properties. This alteration was detected in 1/1893 women with epithelial ovarian cancer from three population-based studies who were tested for mutations in MLH1, MSH2, and MSH6 (Pal T et al. Br. J. Cancer. 2012 Nov;107:1783-90). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Color Health, Inc, SCV001352317.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 30, 2021

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