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NM_000138.5(FBN1):c.3124G>A (p.Gly1042Ser) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 12, 2020
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:
RCV002314188.9

Allele description [Variation Report for NM_000138.5(FBN1):c.3124G>A (p.Gly1042Ser)]

NM_000138.5(FBN1):c.3124G>A (p.Gly1042Ser)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.3124G>A (p.Gly1042Ser)
HGVS:
  • NC_000015.10:g.48488452C>T
  • NG_008805.2:g.162337G>A
  • NM_000138.5:c.3124G>AMANE SELECT
  • NP_000129.3:p.Gly1042Ser
  • NP_000129.3:p.Gly1042Ser
  • LRG_778t1:c.3124G>A
  • LRG_778:g.162337G>A
  • LRG_778p1:p.Gly1042Ser
  • NC_000015.9:g.48780649C>T
  • NM_000138.4:c.3124G>A
Protein change:
G1042S
Links:
dbSNP: rs1555398681
NCBI 1000 Genomes Browser:
rs1555398681
Molecular consequence:
  • NM_000138.5:c.3124G>A - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000738455Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Aug 12, 2020) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.

Sakai H, Visser R, Ikegawa S, Ito E, Numabe H, Watanabe Y, Mikami H, Kondoh T, Kitoh H, Sugiyama R, Okamoto N, Ogata T, Fodde R, Mizuno S, Takamura K, Egashira M, Sasaki N, Watanabe S, Nishimaki S, Takada F, Nagai T, Okada Y, et al.

Am J Med Genet A. 2006 Aug 15;140(16):1719-25.

PubMed [citation]
PMID:
16835936

FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.

Attanasio M, Lapini I, Evangelisti L, Lucarini L, Giusti B, Porciani M, Fattori R, Anichini C, Abbate R, Gensini G, Pepe G.

Clin Genet. 2008 Jul;74(1):39-46. doi: 10.1111/j.1399-0004.2008.01007.x. Epub 2008 Apr 22.

PubMed [citation]
PMID:
18435798
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000738455.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.G1042S variant (also known as c.3124G>A), located in coding exon 25 of the FBN1 gene, results from a G to A substitution at nucleotide position 3124. The glycine at codon 1042 is replaced by serine, an amino acid with similar properties, and is located in the cb EGF-like #11 domain. This alteration was detected in a 30 year old female reported to have Marfan syndrome who had ectopia lentis, pectus carinatum, and pes planus (Attanasio M et al. Clin Genet. 2008;74:39-46). Another alteration affecting this amino acid (p.G1042D, c.3125G>A) was reported in a 2 year old patient who met major cardiovascular and skeletal criteria but who did not fulfill Ghent criteria at the time of study (Sakai H et al. Am J Med Genet A. 2006;140:1719-25). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Oct 13, 2024