NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr) AND Marfan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 3, 2011
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:: RCV000035178.5

Allele description [Variation Report for NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr)]

NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr)

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.368G>A (p.Cys123Tyr)

HGVS:

NC_000015.10:g.48600213C>T
NG_008805.2:g.50576G>A
NM_000138.5:c.368G>AMANE SELECT
NP_000129.3:p.Cys123Tyr
NP_000129.3:p.Cys123Tyr
LRG_778t1:c.368G>A
LRG_778:g.50576G>A
LRG_778p1:p.Cys123Tyr
NC_000015.9:g.48892410C>T
NM_000138.4:c.368G>A
c.368G>A

Protein change:

C123Y

Links:

dbSNP: rs397515794

NCBI 1000 Genomes Browser:

rs397515794

Molecular consequence:

NM_000138.5:c.368G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058820	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jun 3, 2011)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16222657, 18435798, 15983637, 10486319, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000058820

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jun 3, 2011)

germline

clinical testing

PubMed (5)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies.

Arbustini E, Grasso M, Ansaldi S, Malattia C, Pilotto A, Porcu E, Disabella E, Marziliano N, Pisani A, Lanzarini L, Mannarino S, Larizza D, Mosconi M, Antoniazzi E, Zoia MC, Meloni G, Magrassi L, Brega A, Bedeschi MF, Torrente I, Mari F, Tavazzi L.

Hum Mutat. 2005 Nov;26(5):494.

PubMed [citation]

PMID:: 16222657

FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.

Attanasio M, Lapini I, Evangelisti L, Lucarini L, Giusti B, Porciani M, Fattori R, Anichini C, Abbate R, Gensini G, Pepe G.

Clin Genet. 2008 Jul;74(1):39-46. doi: 10.1111/j.1399-0004.2008.01007.x. Epub 2008 Apr 22.

PubMed [citation]

PMID:: 18435798

See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000058820.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

The Cys123Tyr variant has been reported in 3 individuals with a clinical diagnos is of or suspected Marfan syndrome and was absent from 220 control chromosomes ( Arbustini 2005, D'Amore 2005, Attanasio 2008). In addition, this variant affects a cysteine residue. Cysteine substitutions are a common finding in individuals with Marfan syndrome (Schrijver 1999). The Cys123Tyr variant also lies within a functional domain of FBN1 and is likely to be responsible for the clinical featu res observed in this individual. Therefore, this variant is highly likely to be pathogenic.

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

Last Updated: Mar 5, 2025

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