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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922527	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27234404, 27906200, 33844962 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922527

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 7, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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