NM_001999.4(FBN2):c.3486T>G (p.Cys1162Trp) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Jun 15, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000620817.1

Allele description [Variation Report for NM_001999.4(FBN2):c.3486T>G (p.Cys1162Trp)]

NM_001999.4(FBN2):c.3486T>G (p.Cys1162Trp)

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.3486T>G (p.Cys1162Trp)
HGVS:
  • NC_000005.10:g.128338109A>C
  • NG_008750.1:g.204935T>G
  • NM_001999.4:c.3486T>GMANE SELECT
  • NP_001990.2:p.Cys1162Trp
  • NC_000005.9:g.127673801A>C
  • NM_001999.3:c.3486T>G
Protein change:
C1162W
Links:
dbSNP: rs1554123064
NCBI 1000 Genomes Browser:
rs1554123064
Molecular consequence:
  • NM_001999.4:c.3486T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000739034Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Jun 15, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000739034.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.C1162W variant (also known as c.3486T>G), located in coding exon 27 of the FBN2 gene, results from a T to G substitution at nucleotide position 3486. The cysteine at codon 1162 is replaced by tryptophan, an amino acid with highly dissimilar properties. Based on internal structural assessment, this alteration eliminates a structurally critical disulfide bond in cbEGF domain #13. In one study, 13 of 14 reported FBN2 mutations were found in the central 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 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
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 7, 2020

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