NM_000138.5(FBN1):c.4577G>T (p.Cys1526Phe) AND Marfan syndrome

Germline classification:: Uncertain significance (1 submission)
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:: RCV003314337.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4577G>T (p.Cys1526Phe)]

NM_000138.5(FBN1):c.4577G>T (p.Cys1526Phe)

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.4577G>T (p.Cys1526Phe)

HGVS:

NC_000015.10:g.48468417C>A
NG_008805.2:g.182372G>T
NM_000138.5:c.4577G>TMANE SELECT
NM_001406716.1:c.4577G>T
NP_000129.3:p.Cys1526Phe
NP_000129.3:p.Cys1526Phe
NP_001393645.1:p.Cys1526Phe
LRG_778t1:c.4577G>T
LRG_778:g.182372G>T
LRG_778p1:p.Cys1526Phe
NC_000015.9:g.48760614C>A
NM_000138.4:c.4577G>T

Protein change:

C1526F

Molecular consequence:

NM_000138.5:c.4577G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406716.1:c.4577G>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

Recent activity

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cytochrome oxidase subunit III (mitochondrion) [Gallus gallus bankiva]
cytochrome oxidase subunit III (mitochondrion) [Gallus gallus bankiva]
gi|71040228|dbj|BAE16084.1|

Protein
translation elongation factor 1-alpha, partial [Fusarium verticillioides]
translation elongation factor 1-alpha, partial [Fusarium verticillioides]
gi|2574168653|gb|WMV02737.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004013584	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18087243, 19839986, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004013584

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

unknown

clinical testing

PubMed (3)
[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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome? Need for a long-term follow-up.

Pepe G, Lapini I, Evangelisti L, Attanasio M, Giusti B, Lucarini L, Fattori R, Pellicanò G, Scrivanti M, Porciani MC, Abbate R, Gensini GF.

Mol Vis. 2007 Nov 29;13:2242-7.

PubMed [citation]

PMID:: 18087243

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome.

Hung CC, Lin SY, Lee CN, Cheng HY, Lin SP, Chen MR, Chen CP, Chang CH, Lin CY, Yu CC, Chiu HH, Cheng WF, Ho HN, Niu DM, Su YN.

Ann Hum Genet. 2009 Nov;73(Pt 6):559-67. doi: 10.1111/j.1469-1809.2009.00545.x.

PubMed [citation]

PMID:: 19839986

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV004013584.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.99). Different missense changes at the same codon (p.Cys1526Ser, p.Cys1526Tyr) have been reported to be associated with FBN1 related disorder (ClinVar ID: VCV000264314 / PMID: 18087243, 19839986). However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as Uncertain significance according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Jul 22, 2023

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