NM_000138.5(FBN1):c.4588C>T (p.Arg1530Cys) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 16, 2025
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:: RCV000524499.20

Allele description [Variation Report for NM_000138.5(FBN1):c.4588C>T (p.Arg1530Cys)]

NM_000138.5(FBN1):c.4588C>T (p.Arg1530Cys)

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.4588C>T (p.Arg1530Cys)

Other names:

NM_000138.4(FBN1):c.4588C>T(p.Arg1530Cys)

HGVS:

NC_000015.10:g.48468097G>A
NG_008805.2:g.182692C>T
NM_000138.5:c.4588C>TMANE SELECT
NP_000129.3:p.Arg1530Cys
NP_000129.3:p.Arg1530Cys
LRG_778t1:c.4588C>T
LRG_778:g.182692C>T
LRG_778p1:p.Arg1530Cys
NC_000015.9:g.48760294G>A
NM_000138.4:c.4588C>T
c.4588C>T

Protein change:

R1530C

Links:

dbSNP: rs111401431

Molecular consequence:

NM_000138.5:c.4588C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Marfan syndrome (MFS)
Synonyms:: MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000544939	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 16, 2025)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 11700157, 14695540, 17253931, 17627385, 17663468, 17679947, 19863550, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544939

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 16, 2025)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome.

Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A.

Arch Intern Med. 2001 Nov 12;161(20):2447-54.

PubMed [citation]

PMID:: 11700157

Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy.

Biggin A, Holman K, Brett M, Bennetts B, Adès L.

Hum Mutat. 2004 Jan;23(1):99.

PubMed [citation]

PMID:: 14695540

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544939.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1530 of the FBN1 protein (p.Arg1530Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Marfan syndrome (PMID: 11700157, 14695540, 17253931, 17627385, 17663468, 17679947, 19863550). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 36078). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FBN1 protein function with a positive predictive value of 95%. For these reasons, this variant has been 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: Jun 20, 2026

ClinVar

Relating variation to medicine