NM_000179.2(MSH6):c.3469G>T (p.Gly1157Cys) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jan 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001174713.1

Allele description [Variation Report for NM_000179.2(MSH6):c.3469G>T (p.Gly1157Cys)]

NM_000179.2(MSH6):c.3469G>T (p.Gly1157Cys)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.3469G>T (p.Gly1157Cys)
HGVS:
  • NC_000002.12:g.47804940G>T
  • NG_007111.1:g.26794G>T
  • NG_008397.1:g.105736C>A
  • NM_000179.2:c.3469G>T
  • NM_001281492.1:c.3079G>T
  • NM_001281493.1:c.2563G>T
  • NM_001281494.1:c.2563G>T
  • NP_000170.1:p.Gly1157Cys
  • NP_001268421.1:p.Gly1027Cys
  • NP_001268422.1:p.Gly855Cys
  • NP_001268423.1:p.Gly855Cys
  • LRG_219t1:c.3469G>T
  • LRG_219:g.26794G>T
  • LRG_219p1:p.Gly1157Cys
  • NC_000002.11:g.48032079G>T
  • p.G1157C
Protein change:
G1027C
Links:
dbSNP: rs587779264
NCBI 1000 Genomes Browser:
rs587779264
Molecular consequence:
  • NM_000179.2:c.3469G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.1:c.3079G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.1:c.2563G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.1:c.2563G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001337984Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jan 27, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

Johnson A, Severson E, Gay L, Vergilio JA, Elvin J, Suh J, Daniel S, Covert M, Frampton GM, Hsu S, Lesser GJ, Stogner-Underwood K, Mott RT, Rush SZ, Stanke JJ, Dahiya S, Sun J, Reddy P, Chalmers ZR, Erlich R, Chudnovsky Y, Fabrizio D, et al.

Oncologist. 2017 Dec;22(12):1478-1490. doi: 10.1634/theoncologist.2017-0242. Epub 2017 Sep 14.

PubMed [citation]
PMID:
28912153
PMCID:
PMC5728033

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337984.1

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

Description

Variant summary: MSH6 c.3469G>T (p.Gly1157Cys) results in a non-conservative amino acid change located in the C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251390 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, there are no reports of c.3469G>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating an impact on protein function in the literature. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jun 18, 2021

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