NM_000138.5(FBN1):c.6032G>A (p.Cys2011Tyr) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Sep 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001260318.1

Allele description [Variation Report for NM_000138.5(FBN1):c.6032G>A (p.Cys2011Tyr)]

NM_000138.5(FBN1):c.6032G>A (p.Cys2011Tyr)

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.6032G>A (p.Cys2011Tyr)
HGVS:
  • NC_000015.10:g.48444546C>T
  • NG_008805.2:g.206243G>A
  • NM_000138.4:c.6032G>A
  • NM_000138.5:c.6032G>AMANE SELECT
  • NP_000129.3:p.Cys2011Tyr
  • NP_000129.3:p.Cys2011Tyr
  • LRG_778t1:c.6032G>A
  • LRG_778:g.206243G>A
  • LRG_778p1:p.Cys2011Tyr
  • NC_000015.9:g.48736743C>T
Protein change:
C2011Y
Links:
dbSNP: rs886038967
NCBI 1000 Genomes Browser:
rs886038967
Molecular consequence:
  • NM_000138.4:c.6032G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000138.5:c.6032G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001437243Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Sep 16, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001437243.1

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

Description

Variant summary: FBN1 c.6032G>A (p.Cys2011Tyr) results in a non-conservative amino acid change located in the EGF-like calcium-binding domain (IPR001881) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251146 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6032G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, missense mutations affecting or creating cysteine residues or located within the conserved resides of the EGF consensus sequence are listed among the criteria for a causal FBN1 mutation when identified as de-novo (with proven paternity) in the revised Ghent criteria for the diagnosis of Marfan and related conditions (Loeys, BL et al, 2010). Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Oct 25, 2021

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