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NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 27, 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:
RCV002310634.9

Allele description [Variation Report for NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter)]

NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter)

Gene:
SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.2
Genomic location:
Preferred name:
NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter)
HGVS:
  • NC_000018.10:g.51076662C>T
  • NG_013013.2:g.113623C>T
  • NM_005359.6:c.1333C>TMANE SELECT
  • NP_005350.1:p.Arg445Ter
  • NP_005350.1:p.Arg445Ter
  • LRG_318t1:c.1333C>T
  • LRG_318:g.113623C>T
  • LRG_318p1:p.Arg445Ter
  • NC_000018.9:g.48603032C>T
  • NM_005359.5:c.1333C>T
  • p.R445*
Protein change:
R445*; ARG445TER
Links:
OMIM: 600993.0014; dbSNP: rs377767360
NCBI 1000 Genomes Browser:
rs377767360
Molecular consequence:
  • NM_005359.6:c.1333C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086
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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000214483Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 27, 2021) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV000214483.7

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

Description

The p.R445* pathogenic mutation (also known as c.1333C>T), located in coding exon 10 of the SMAD4 gene, results from a C to T substitution at nucleotide position 1333. This changes the amino acid from an arginine to a stop codon within coding exon 10. This mutation has been identified in multiple individuals with Juvenile Polyposis Syndrome (JPS) (Woodford-Richens K et al. Gut. 2000 May;46:656-60; Heald B et al. Am. J. Med. Genet. A. 2015 Aug;167A:1758-62; Handra-Luca A et al. Am. J. Med. Genet. A. 2005 Oct;138A:113-7). This mutation has also been reported in a patient with lower grade glioma from a cohort of 4034 cancer cases from The Cancer Genome Atlas (Lu C et al. Nat Commun, 2015 Dec;6:10086). Of note, this alteration is also designated as c.1363C>T in published literature. 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: Aug 25, 2024