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NM_000138.5(FBN1):c.4226_4227del (p.Cys1408_Ser1409insTer) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 16, 2019
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:
RCV001193501.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4226_4227del (p.Cys1408_Ser1409insTer)]

NM_000138.5(FBN1):c.4226_4227del (p.Cys1408_Ser1409insTer)

Genes:
LOC126862124:CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48764566-48765765 [Gene]
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.4226_4227del (p.Cys1408_Ser1409insTer)
HGVS:
  • NC_000015.10:g.48472660AG[1]
  • NC_000015.9:g.48764857_48764858del
  • NG_008805.2:g.178126CT[1]
  • NM_000138.5:c.4226_4227delMANE SELECT
  • NP_000129.3:p.Cys1408_Ser1409insTer
  • LRG_778t1:c.4226_4227del
  • LRG_778:g.178126CT[1]
  • NC_000015.9:g.48764857AG[1]
  • NC_000015.9:g.48764857_48764858del
  • NC_000015.9:g.48764857_48764858delAG
  • NM_000138.4:c.4226_4227del
  • NM_000138.4:c.4226_4227delCT
  • p.Ser1409*
Links:
dbSNP: rs1566905976
NCBI 1000 Genomes Browser:
rs1566905976
Molecular consequence:
  • NM_000138.5:c.4226_4227del - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001362383Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Sep 16, 2019) 		germlineclinical testing

Citation Link

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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, SCV001362383.1

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

Description

Variant summary: FBN1 c.4226_4227delCT (p.Ser1409X) 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 (eg. c.4621C>T, p.Arg1541X; c.4930C>T, p.Arg1644X). The variant was absent in 251442 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4226_4227delCT in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. 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: Sep 29, 2024