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NM_002439.5(MSH3):c.1035del (p.Pro346_Leu347insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 28, 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:
RCV001017087.4

Allele description [Variation Report for NM_002439.5(MSH3):c.1035del (p.Pro346_Leu347insTer)]

NM_002439.5(MSH3):c.1035del (p.Pro346_Leu347insTer)

Gene:
MSH3:mutS homolog 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
5q14.1
Genomic location:
Preferred name:
NM_002439.5(MSH3):c.1035del (p.Pro346_Leu347insTer)
HGVS:
  • NC_000005.10:g.80674990del
  • NG_016607.2:g.25516del
  • NM_002439.5:c.1035delMANE SELECT
  • NP_002430.3:p.Pro346_Leu347insTer
  • NC_000005.9:g.79970809del
  • NG_016607.1:g.25516del
  • NM_002439.3:c.1035delT
  • NM_002439.4:c.1035del
Links:
dbSNP: rs1580553607
NCBI 1000 Genomes Browser:
rs1580553607
Molecular consequence:
  • NM_002439.5:c.1035del - 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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001178113Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 28, 2021) 		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

Loss of MSH2 and MSH6 due to heterozygous germline defects in MSH3 and MSH6.

Morak M, Käsbauer S, Kerscher M, Laner A, Nissen AM, Benet-Pagès A, Schackert HK, Keller G, Massdorf T, Holinski-Feder E.

Fam Cancer. 2017 Oct;16(4):491-500. doi: 10.1007/s10689-017-9975-z.

PubMed [citation]
PMID:
28528517

Details of each submission

From Ambry Genetics, SCV001178113.4

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

Description

The c.1035delT pathogenic mutation, located in coding exon 7 of the MSH3 gene, results from a deletion of one nucleotide at nucleotide position 1035, causing a translational frameshift with a predicted alternate stop codon (p.L347*). This alteration has been previously identified in an individual meeting Amsterdam criteria who was also found to carry the MSH6 pathogenic mutation c.3969_3979delTGAGAAGATGA (Morak M et al. Fam. Cancer, 2017 Oct;16:491-500). 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 20, 2024