NM_000138.5(FBN1):c.4588C>T (p.Arg1530Cys) AND FBN1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 2, 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:: RCV004532413.1

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:: FBN1-related disorder
Synonyms:: FBN1-related disorders
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004111480	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004111480

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 2, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004111480.1

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

Description

The FBN1 c.4588C>T variant is predicted to result in the amino acid substitution p.Arg1530Cys. This variant has been reported in multiple individuals with ectopia lentis, and in some cases was determined to have arisen de novo (see for examples Loeys et al. 2001. PubMed ID: 11700157; Khan et al. 2014. PubMed ID: 24698609; Li et al. 2019. PubMed ID: 31098894). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Given the evidence, we interpret c.4588C>T (p.Arg1530Cys) 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

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