U.S. flag

An official website of the United States government

NM_000138.5(FBN1):c.4172G>A (p.Cys1391Tyr) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 7, 2023
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:
RCV003226371.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4172G>A (p.Cys1391Tyr)]

NM_000138.5(FBN1):c.4172G>A (p.Cys1391Tyr)

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.4172G>A (p.Cys1391Tyr)
HGVS:
  • NC_000015.10:g.48474293C>T
  • NG_008805.2:g.176496G>A
  • NM_000138.5:c.4172G>AMANE SELECT
  • NP_000129.3:p.Cys1391Tyr
  • NP_000129.3:p.Cys1391Tyr
  • LRG_778t1:c.4172G>A
  • LRG_778:g.176496G>A
  • LRG_778p1:p.Cys1391Tyr
  • NC_000015.9:g.48766490C>T
  • NM_000138.4:c.4172G>A
Protein change:
C1391Y
Links:
dbSNP: rs1352478541
NCBI 1000 Genomes Browser:
rs1352478541
Molecular consequence:
  • NM_000138.5:c.4172G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003922527Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Mar 7, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

Yang H, Luo M, Chen Q, Fu Y, Zhang J, Qian X, Sun X, Fan Y, Zhou Z, Chang Q.

Clin Chim Acta. 2016 Aug 1;459:30-35. doi: 10.1016/j.cca.2016.05.021. Epub 2016 May 24.

PubMed [citation]
PMID:
27234404

Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.

Groth KA, Von Kodolitsch Y, Kutsche K, Gaustadnes M, Thorsen K, Andersen NH, Gravholt CH.

Genet Med. 2017 Jul;19(7):772-777. doi: 10.1038/gim.2016.181. Epub 2016 Dec 1.

PubMed [citation]
PMID:
27906200
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922527.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: FBN1 c.4172G>A (p.Cys1391Tyr) results in a non-conservative amino acid change located in the EGF-like domain 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 251348 control chromosomes. c.4172G>A has been reported in the literature in individuals affected with Marfan Syndrome. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 29, 2024