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NM_000179.3(MSH6):c.2238dup (p.Leu747fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 8, 2019
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:
RCV002431514.2

Allele description [Variation Report for NM_000179.3(MSH6):c.2238dup (p.Leu747fs)]

NM_000179.3(MSH6):c.2238dup (p.Leu747fs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.2238dup (p.Leu747fs)
HGVS:
  • NC_000002.12:g.47800221dup
  • NG_007111.1:g.22075dup
  • NM_000179.3:c.2238dupMANE SELECT
  • NM_001281492.2:c.1848dup
  • NM_001281493.2:c.1332dup
  • NM_001281494.2:c.1332dup
  • NP_000170.1:p.Leu747fs
  • NP_000170.1:p.Leu747fs
  • NP_001268421.1:p.Leu617fs
  • NP_001268422.1:p.Leu445fs
  • NP_001268423.1:p.Leu445fs
  • LRG_219t1:c.2238dup
  • LRG_219:g.22075dup
  • LRG_219p1:p.Leu747fs
  • NC_000002.11:g.48027355_48027356insT
  • NC_000002.11:g.48027360dup
  • NM_000179.2:c.2238dup
  • NM_000179.2:c.2238dupT
Protein change:
L445fs
Links:
dbSNP: rs1553413599
NCBI 1000 Genomes Browser:
rs1553413599
Molecular consequence:
  • NM_000179.3:c.2238dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.1848dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.1332dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.1332dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002730969Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 8, 2019) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency.

Tesch VK, IJspeert H, Raicht A, Rueda D, Dominguez-Pinilla N, Allende LM, Colas C, Rosenbaum T, Ilencikova D, Baris HN, Nathrath MHM, Suerink M, Januszkiewicz-Lewandowska D, Ragab I, Azizi AA, Wenzel SS, Zschocke J, Schwinger W, Kloor M, Blattmann C, Brugieres L, van der Burg M, et al.

Front Immunol. 2018;9:1506. doi: 10.3389/fimmu.2018.01506.

PubMed [citation]
PMID:
30013564
PMCID:
PMC6036136

Details of each submission

From Ambry Genetics, SCV002730969.2

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

Description

The c.2238dupT variant, located in coding exon 4 of the MSH6 gene, results from a duplication of T at nucleotide position 2238, causing a translational frameshift with a predicted alternate stop codon (p.L747Sfs*9). This mutation has been reported in conjunction with another MSH6 alteration in a patient who was diagnosed with medulloblastoma at age 6 and who was also found to have a cafe au lait macule (Tesch VK et al. Front Immunol, 2018 Jul;9:1506). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 8, 2024