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NM_000179.3(MSH6):c.2348_2349del (p.Leu782_Cys783insTer) AND Endometrial carcinoma

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Jul 31, 2021
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:
RCV001353421.4

Allele description [Variation Report for NM_000179.3(MSH6):c.2348_2349del (p.Leu782_Cys783insTer)]

NM_000179.3(MSH6):c.2348_2349del (p.Leu782_Cys783insTer)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.2348_2349del (p.Leu782_Cys783insTer)
HGVS:
  • NC_000002.12:g.47800331_47800332del
  • NG_007111.1:g.22185_22186del
  • NM_000179.3:c.2348_2349delMANE SELECT
  • NM_001281492.2:c.1958_1959del
  • NM_001281493.2:c.1442_1443del
  • NM_001281494.2:c.1442_1443del
  • NP_000170.1:p.Leu782_Cys783insTer
  • NP_001268421.1:p.Leu652_Cys653insTer
  • NP_001268422.1:p.Leu480_Cys481insTer
  • NP_001268423.1:p.Leu480_Cys481insTer
  • LRG_219:g.22185_22186del
  • NC_000002.11:g.48027469_48027470del
  • NC_000002.11:g.48027470_48027471del
  • NM_000179.2:c.2348_2349delGT
Links:
dbSNP: rs267608065
NCBI 1000 Genomes Browser:
rs267608065
Molecular consequence:
  • NM_000179.3:c.2348_2349del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.2:c.1958_1959del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.2:c.1442_1443del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.2:c.1442_1443del - nonsense - [Sequence Ontology: SO:0001587]
Observations:
3

Condition(s)

Name:
Endometrial carcinoma
Synonyms:
Endometrial carcinoma, somatic
Identifiers:
MONDO: MONDO:0002447; MedGen: C0476089; OMIM: 608089; Human Phenotype Ontology: HP:0012114

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000592607Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Pathogenicunknownclinical testing

SCV003804328CZECANCA consortium
no assertion criteria provided
Pathogenic
(Feb 21, 2023) 		germlineclinical testing

SCV004196365Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 31, 2021) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyes2not providednot providednot providednot providedclinical testing
Slavicgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592607.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided

Description

The MSH6 p.Cys783X variant was identified in individuals with HNPCC although no frequency data was provided (Steinke 2008, Talseth-Palmer 2010). The variant was also identified in dbSNP (ID: rs267608065) “With pathogenic allele”, the Clinvitae database as pathogenic, InSiGHT Colon Cancer Gene Variant Database as pathogenic, the ClinVar database (classified as a pathogenic variant and reviewed by an expert panel). The p.Cys783X variant leads to a premature stop codon at position 783, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in Lynch syndrome and this is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided2not providednot providednot provided

From CZECANCA consortium, SCV003804328.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Slavic1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Baylor Genetics, SCV004196365.1

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

Last Updated: Oct 8, 2024