NM_000138.5(FBN1):c.4243dup (p.Cys1415fs) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Clinical significance:Likely pathogenic (Last evaluated: Aug 10, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001255474.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4243dup (p.Cys1415fs)]

NM_000138.5(FBN1):c.4243dup (p.Cys1415fs)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.4243dup (p.Cys1415fs)
HGVS:
  • NC_000015.10:g.48472644dup
  • NG_008805.2:g.178145dup
  • NM_000138.5:c.4243dupMANE SELECT
  • NP_000129.3:p.Cys1415fs
  • LRG_778t1:c.4243dup
  • LRG_778:g.178145dup
  • NC_000015.9:g.48764841dup
  • NC_000015.9:g.48764841dupA
  • NM_000138.4:c.4243dupT
Protein change:
C1415fs
Links:
Molecular consequence:
  • NM_000138.5:c.4243dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Identifiers:
MedGen: CN229799

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001431891Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Aug 10, 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, SCV001431891.1

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

Description

Variant summary: FBN1 c.4243dupT (p.Cys1415LeufsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251416 control chromosomes. To our knowledge, no occurrence of c.4243dupT in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jun 14, 2021

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