NM_001999.4(FBN2):c.3593G>A (p.Cys1198Tyr) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 2022
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:: RCV002336530.2

Allele description [Variation Report for NM_001999.4(FBN2):c.3593G>A (p.Cys1198Tyr)]

NM_001999.4(FBN2):c.3593G>A (p.Cys1198Tyr)

Gene:

FBN2:fibrillin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q23.3

Genomic location:

Preferred name:

NM_001999.4(FBN2):c.3593G>A (p.Cys1198Tyr)

HGVS:

NC_000005.10:g.128338002C>T
NG_008750.1:g.205042G>A
NM_001999.4:c.3593G>AMANE SELECT
NP_001990.2:p.Cys1198Tyr
NC_000005.9:g.127673694C>T
NM_001999.3:c.3593G>A
P35556:p.Cys1198Tyr
p.C1198Y

Protein change:

C1198Y

Links:

UniProtKB: P35556#VAR_054984; dbSNP: rs863223567

NCBI 1000 Genomes Browser:

rs863223567

Molecular consequence:

NM_001999.4:c.3593G>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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Gnaphalieae internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA ...
Gnaphalieae internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence.
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002619433	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002619433

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 17, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ten novel FBN2 mutations in congenital contractural arachnodactyly: delineation of the molecular pathogenesis and clinical phenotype.

Gupta PA, Putnam EA, Carmical SG, Kaitila I, Steinmann B, Child A, Danesino C, Metcalfe K, Berry SA, Chen E, Delorme CV, Thong MK, Adès LC, Milewicz DM.

Hum Mutat. 2002 Jan;19(1):39-48.

PubMed [citation]

PMID:: 11754102

Details of each submission

From Ambry Genetics, SCV002619433.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The p.C1198Y variant (also known as c.3593G>A), located in coding exon 27 of the FBN2 gene, results from a G to A substitution at nucleotide position 3593. The cysteine at codon 1198 is replaced by tyrosine, an amino acid with highly dissimilar properties. In one study, 13 of 14 reported FBN2 mutations were found in the middle region of the gene (exons 24-36), and 7 of these mutations were noted to alter or produce a cysteine residue (Callewaert BL et al. Hum Mutat. 2009;30(3):334-341). This alteration has been reported in a congenital contracture arachnodactyly (CCA) cohort (Gupta PA et al. Hum Mutat, 2002 Jan;19:39-48). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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