NM_000138.5(FBN1):c.4172G>T (p.Cys1391Phe) AND FBN1-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 4, 2024
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV004530696.2

Allele description [Variation Report for NM_000138.5(FBN1):c.4172G>T (p.Cys1391Phe)]

NM_000138.5(FBN1):c.4172G>T (p.Cys1391Phe)

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>T (p.Cys1391Phe)

HGVS:

NC_000015.10:g.48474293C>A
NG_008805.2:g.176496G>T
NM_000138.4:c.4172G>T
NM_000138.5:c.4172G>TMANE SELECT
NP_000129.3:p.Cys1391Phe
LRG_778t1:c.4172G>T
LRG_778:g.176496G>T
NC_000015.9:g.48766490C>A

Protein change:

C1391F

Links:

dbSNP: rs1352478541

NCBI 1000 Genomes Browser:

rs1352478541

Molecular consequence:

NM_000138.5:c.4172G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: FBN1-related disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004739547	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Likely pathogenic (Mar 4, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004739547

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Likely pathogenic
(Mar 4, 2024)

germline

clinical testing

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004739547.2

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

Description

The FBN1 c.4172G>T variant is predicted to result in the amino acid substitution p.Cys1391Phe. This variant was reported within individuals presenting with Marfan syndrome, however inheritance information was not provided (Rybczynski et al. 2008. PubMed ID: 19012347; Supplementary Data, Stark et al. 2020. PubMed ID: 32679894). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Of note, this variant was reported as de novo in one patient with clinical features consistent with Marfan syndrome (Internal Data, PreventionGenetics). This variant is interpreted as likely 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: Nov 10, 2024

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