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NM_000251.3(MSH2):c.2345C>T (p.Thr782Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 7, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002428532.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2345C>T (p.Thr782Ile)]

NM_000251.3(MSH2):c.2345C>T (p.Thr782Ile)

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.2345C>T (p.Thr782Ile)
HGVS:
  • NC_000002.12:g.47478406C>T
  • NG_007110.2:g.80283C>T
  • NM_000251.3:c.2345C>TMANE SELECT
  • NM_001258281.1:c.2147C>T
  • NM_001406631.1:c.2345C>T
  • NM_001406632.1:c.2345C>T
  • NM_001406633.1:c.2345C>T
  • NM_001406634.1:c.2345C>T
  • NM_001406635.1:c.2345C>T
  • NM_001406636.1:c.2312C>T
  • NM_001406637.1:c.2345C>T
  • NM_001406638.1:c.2384C>T
  • NM_001406639.1:c.2345C>T
  • NM_001406640.1:c.2345C>T
  • NM_001406641.1:c.2345C>T
  • NM_001406642.1:c.2345C>T
  • NM_001406643.1:c.2345C>T
  • NM_001406644.1:c.2345C>T
  • NM_001406645.1:c.2345C>T
  • NM_001406646.1:c.2345C>T
  • NM_001406647.1:c.2195C>T
  • NM_001406648.1:c.2345C>T
  • NM_001406649.1:c.2195C>T
  • NM_001406650.1:c.2195C>T
  • NM_001406651.1:c.2195C>T
  • NM_001406652.1:c.2195C>T
  • NM_001406653.1:c.2285C>T
  • NM_001406654.1:c.1925C>T
  • NM_001406656.1:c.1448C>T
  • NM_001406658.1:c.989C>T
  • NM_001406659.1:c.989C>T
  • NM_001406660.1:c.989C>T
  • NM_001406661.1:c.989C>T
  • NM_001406662.1:c.989C>T
  • NM_001406669.1:c.989C>T
  • NM_001406674.1:c.2345C>T
  • NP_000242.1:p.Thr782Ile
  • NP_000242.1:p.Thr782Ile
  • NP_001245210.1:p.Thr716Ile
  • NP_001393560.1:p.Thr782Ile
  • NP_001393561.1:p.Thr782Ile
  • NP_001393562.1:p.Thr782Ile
  • NP_001393563.1:p.Thr782Ile
  • NP_001393564.1:p.Thr782Ile
  • NP_001393565.1:p.Thr771Ile
  • NP_001393566.1:p.Thr782Ile
  • NP_001393567.1:p.Thr795Ile
  • NP_001393568.1:p.Thr782Ile
  • NP_001393569.1:p.Thr782Ile
  • NP_001393570.1:p.Thr782Ile
  • NP_001393571.1:p.Thr782Ile
  • NP_001393572.1:p.Thr782Ile
  • NP_001393573.1:p.Thr782Ile
  • NP_001393574.1:p.Thr782Ile
  • NP_001393575.1:p.Thr782Ile
  • NP_001393576.1:p.Thr732Ile
  • NP_001393577.1:p.Thr782Ile
  • NP_001393578.1:p.Thr732Ile
  • NP_001393579.1:p.Thr732Ile
  • NP_001393580.1:p.Thr732Ile
  • NP_001393581.1:p.Thr732Ile
  • NP_001393582.1:p.Thr762Ile
  • NP_001393583.1:p.Thr642Ile
  • NP_001393585.1:p.Thr483Ile
  • NP_001393587.1:p.Thr330Ile
  • NP_001393588.1:p.Thr330Ile
  • NP_001393589.1:p.Thr330Ile
  • NP_001393590.1:p.Thr330Ile
  • NP_001393591.1:p.Thr330Ile
  • NP_001393598.1:p.Thr330Ile
  • NP_001393603.1:p.Thr782Ile
  • LRG_218t1:c.2345C>T
  • LRG_218:g.80283C>T
  • LRG_218p1:p.Thr782Ile
  • NC_000002.11:g.47705545C>T
  • NM_000251.1:c.2345C>T
  • NM_000251.2:c.2345C>T
  • NR_176230.1:n.2381C>T
  • NR_176231.1:n.2349C>T
  • NR_176232.1:n.2381C>T
  • NR_176233.1:n.2223C>T
  • NR_176234.1:n.2381C>T
  • NR_176235.1:n.2381C>T
  • NR_176236.1:n.2381C>T
  • NR_176237.1:n.2381C>T
  • NR_176238.1:n.2514C>T
  • NR_176239.1:n.2381C>T
  • NR_176240.1:n.2176C>T
  • NR_176241.1:n.2381C>T
  • NR_176242.1:n.2381C>T
  • NR_176243.1:n.2231C>T
  • NR_176244.1:n.2381C>T
  • NR_176245.1:n.2381C>T
  • NR_176246.1:n.2381C>T
  • NR_176247.1:n.2381C>T
  • NR_176248.1:n.2381C>T
  • NR_176249.1:n.2611C>T
  • NR_176250.1:n.2121C>T
Protein change:
T330I
Molecular consequence:
  • NM_000251.3:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.2147C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406631.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406632.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406633.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406634.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406635.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406636.1:c.2312C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406637.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406638.1:c.2384C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406639.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406640.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406641.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406642.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406643.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406644.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406645.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406646.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406647.1:c.2195C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406648.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406649.1:c.2195C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406650.1:c.2195C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406651.1:c.2195C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406652.1:c.2195C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406653.1:c.2285C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406654.1:c.1925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406656.1:c.1448C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406658.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406659.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406660.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406661.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406662.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406669.1:c.989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406674.1:c.2345C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002731882Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Sep 7, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]
PMID:
25186627

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO.

Am J Hum Genet. 2021 Jan 7;108(1):163-175. doi: 10.1016/j.ajhg.2020.12.003. Epub 2020 Dec 23.

PubMed [citation]
PMID:
33357406
PMCID:
PMC7820803

Details of each submission

From Ambry Genetics, SCV002731882.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.T782I variant (also known as c.2345C>T), located in coding exon 14 of the MSH2 gene, results from a C to T substitution at nucleotide position 2345. The threonine at codon 782 is replaced by isoleucine, an amino acid with similar properties. This variant was observed in an individual with early onset-breast cancer amongst a cohort of 1781 non-Ashkenazi Jewish individuals undergoing BRCA1/2 gene testing based on a personal history of breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33). 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.

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

Last Updated: Sep 29, 2024