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NM_000179.3(MSH6):c.3952A>T (p.Arg1318Ter) AND Lynch syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 14, 2017
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:
RCV000826178.4

Allele description [Variation Report for NM_000179.3(MSH6):c.3952A>T (p.Arg1318Ter)]

NM_000179.3(MSH6):c.3952A>T (p.Arg1318Ter)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3952A>T (p.Arg1318Ter)
HGVS:
  • NC_000002.12:g.47806602A>T
  • NG_007111.1:g.28456A>T
  • NG_008397.1:g.104074T>A
  • NM_000179.3:c.3952A>TMANE SELECT
  • NM_001281492.2:c.3562A>T
  • NM_001281493.2:c.3046A>T
  • NM_001281494.2:c.3046A>T
  • NP_000170.1:p.Arg1318Ter
  • NP_001268421.1:p.Arg1188Ter
  • NP_001268422.1:p.Arg1016Ter
  • NP_001268423.1:p.Arg1016Ter
  • LRG_219t1:c.3952A>T
  • LRG_219:g.28456A>T
  • NC_000002.11:g.48033741A>T
  • NM_000179.2:c.3952A>T
  • p.Arg1318X
Protein change:
R1016*
Links:
dbSNP: rs1572747685
NCBI 1000 Genomes Browser:
rs1572747685
Molecular consequence:
  • NM_000179.3:c.3952A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.2:c.3562A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.2:c.3046A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.2:c.3046A>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000967717Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Likely pathogenic
(Dec 14, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967717.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Arg1318X variant in MSH6 has not been previously reported in individuals w ith MSH6-associated cancers and was absent from large population studies. This n onsense variant leads to a premature termination codon at position 1318. This te rmination codon occurs within the terminal 50 bases of the second to last exon a nd is more likely to escape nonsense mediated decay (NMD), resulting in a trunca ted protein. Truncating variants downstream of this variant have been reported i n individuals with Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg1318X variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_Strong; PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Oct 8, 2024