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NM_002439.5(MSH3):c.220C>T (p.Gln74Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 2, 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:
RCV002425838.2

Allele description [Variation Report for NM_002439.5(MSH3):c.220C>T (p.Gln74Ter)]

NM_002439.5(MSH3):c.220C>T (p.Gln74Ter)

Genes:
DHFR:dihydrofolate reductase [Gene - OMIM - HGNC]
MSH3:mutS homolog 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q14.1
Genomic location:
Preferred name:
NM_002439.5(MSH3):c.220C>T (p.Gln74Ter)
HGVS:
  • NC_000005.10:g.80654947C>T
  • NG_016607.2:g.5473C>T
  • NG_023304.1:g.5035G>A
  • NG_105205.1:g.543C>T
  • NG_105205.2:g.570C>T
  • NM_000791.4:c.-458G>AMANE SELECT
  • NM_001290354.2:c.-564G>A
  • NM_001290357.2:c.-458G>A
  • NM_002439.5:c.220C>TMANE SELECT
  • NP_002430.3:p.Gln74Ter
  • NC_000005.9:g.79950766C>T
  • NM_002439.3:c.220C>T
  • NR_110936.2:n.37G>A
Protein change:
Q74*
Molecular consequence:
  • NM_000791.4:c.-458G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001290354.2:c.-564G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001290357.2:c.-458G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NR_110936.2:n.37G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_002439.5:c.220C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002730804Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 2, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002730804.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.Q74* pathogenic mutation (also known as c.220C>T), located in coding exon 1 of the MSH3 gene, results from a C to T substitution at nucleotide position 220. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on internal structural assessment using published crystal structures, use of the alternative initiation codon at M115 would result in a protein missing the functionally important PCNA recognition motif at residues 21-28 (Iyer RR et al. J Biol Chem, 2010 Apr;285:11730-9). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 1, 2024