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NM_005359.6(SMAD4):c.2T>C (p.Met1Thr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 27, 2023
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:
RCV004560050.1

Allele description [Variation Report for NM_005359.6(SMAD4):c.2T>C (p.Met1Thr)]

NM_005359.6(SMAD4):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)
HGVS:
  • NC_000018.10:g.51047048T>C
  • NG_013013.2:g.84009T>C
  • NM_001407041.1:c.2T>C
  • NM_001407042.1:c.2T>C
  • NM_001407043.1:c.2T>C
  • NM_005359.6:c.2T>CMANE SELECT
  • NP_001393970.1:p.Met1Thr
  • NP_001393971.1:p.Met1Thr
  • NP_001393972.1:p.Met1Thr
  • NP_005350.1:p.Met1Thr
  • NP_005350.1:p.Met1Thr
  • LRG_318t1:c.2T>C
  • LRG_318:g.84009T>C
  • LRG_318p1:p.Met1Thr
  • NC_000018.9:g.48573418T>C
  • NM_005359.5:c.2T>C
  • NR_176264.1:n.540T>C
  • NR_176265.1:n.540T>C
Protein change:
M1T
Molecular consequence:
  • NM_005359.6:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407041.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407042.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407043.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005359.6:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005048478Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 27, 2023) 		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, SCV005048478.1

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

Description

The p.M1? variant (also known as c.2T>C) is located in coding exon 1 of the SMAD4 gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). Variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however, there are two alternate in-frame methionine 4, and 24 amino acids from the initiation site, which may result in N-terminal truncation of unknown functional significance. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024