NM_000179.3(MSH6):c.3850dup (p.Thr1284fs) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Jul 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001380321.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)]

NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)
HGVS:
  • NC_000002.12:g.47806500dup
  • NG_007111.1:g.28354dup
  • NG_008397.1:g.104176dup
  • NM_000179.2:c.3850dup
  • NM_000179.3:c.3850dupMANE SELECT
  • NM_001281492.2:c.3460dup
  • NM_001281493.2:c.2944dup
  • NM_001281494.2:c.2944dup
  • NP_000170.1:p.Thr1284fs
  • NP_000170.1:p.Thr1284fs
  • NP_001268421.1:p.Thr1154fs
  • NP_001268422.1:p.Thr982fs
  • NP_001268423.1:p.Thr982fs
  • LRG_219t1:c.3850dup
  • LRG_219:g.28354dup
  • LRG_219p1:p.Thr1284fs
  • NC_000002.11:g.48033638_48033639insA
  • NC_000002.11:g.48033639dup
  • NM_000179.2:c.3850dupA
Protein change:
T1154fs
Links:
dbSNP: rs1553333421
NCBI 1000 Genomes Browser:
rs1553333421
Molecular consequence:
  • NM_000179.3:c.3850dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.3460dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001578324Invitaecriteria provided, single submitter
Pathogenic
(Jul 14, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Devlin LA, Graham CA, Price JH, Morrison PJ.

Ulster Med J. 2008 Jan;77(1):25-30.

PubMed [citation]
PMID:
18269114
PMCID:
PMC2397009

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]
PMID:
24362816
PMCID:
PMC4294709
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001578324.1

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

Description

This sequence change creates a premature translational stop signal (p.Thr1284Asnfs*5) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 433926). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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