U.S. flag

An official website of the United States government

NM_000251.3(MSH2):c.806C>T (p.Ser269Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 11, 2023
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:
RCV002415568.3

Allele description [Variation Report for NM_000251.3(MSH2):c.806C>T (p.Ser269Leu)]

NM_000251.3(MSH2):c.806C>T (p.Ser269Leu)

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.806C>T (p.Ser269Leu)
HGVS:
  • NC_000002.12:g.47414282C>T
  • NG_007110.2:g.16159C>T
  • NM_000251.3:c.806C>TMANE SELECT
  • NM_001258281.1:c.608C>T
  • NP_000242.1:p.Ser269Leu
  • NP_000242.1:p.Ser269Leu
  • NP_001245210.1:p.Ser203Leu
  • LRG_218t1:c.806C>T
  • LRG_218:g.16159C>T
  • LRG_218p1:p.Ser269Leu
  • NC_000002.11:g.47641421C>T
  • NM_000251.1:c.806C>T
  • NM_000251.2:c.806C>T
Protein change:
S203L
Links:
dbSNP: rs63750058
NCBI 1000 Genomes Browser:
rs63750058
Molecular consequence:
  • NM_000251.3:c.806C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.608C>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002677563Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Sep 11, 2023) 		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

Mechanism of mismatch recognition revealed by human MutSĪ² bound to unpaired DNA loops.

Gupta S, Gellert M, Yang W.

Nat Struct Mol Biol. 2011 Dec 18;19(1):72-8. doi: 10.1038/nsmb.2175.

PubMed [citation]
PMID:
22179786
PMCID:
PMC3252464

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, SCV002677563.3

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

Description

The p.S269L variant (also known as c.806C>T), located in coding exon 5 of the MSH2 gene, results from a C to T substitution at nucleotide position 806. The serine at codon 269 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been observed in at least one individual whose colorectal tumor demonstrated loss of MSH2 expression on immunohistochemistry (IHC) and family history was consistent with Lynch syndrome (Ambry internal data). In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally deleterious (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability of the protein (Gupta S et al. Nat. Struct. Mol. Biol., 2011 Dec;19:72-8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024