NM_000138.5(FBN1):c.6629G>A (p.Cys2210Tyr) AND Marfan syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 7, 2019
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:: RCV004017910.1

Allele description [Variation Report for NM_000138.5(FBN1):c.6629G>A (p.Cys2210Tyr)]

NM_000138.5(FBN1):c.6629G>A (p.Cys2210Tyr)

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.6629G>A (p.Cys2210Tyr)

HGVS:

NC_000015.10:g.48432976C>T
NG_008805.2:g.217813G>A
NM_000138.5:c.6629G>AMANE SELECT
NP_000129.3:p.Cys2210Tyr
LRG_778t1:c.6629G>A
LRG_778:g.217813G>A
NC_000015.9:g.48725173C>T
NC_000015.9:g.48725173C>T
NM_000138.4:c.6629G>A

Protein change:

C2210Y

Links:

dbSNP: rs2141235242

NCBI 1000 Genomes Browser:

rs2141235242

Molecular consequence:

NM_000138.5:c.6629G>A - 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

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
SCV004847652	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Mar 7, 2019)	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

SCV004847652

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Mar 7, 2019)

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847652.1

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

Description

The p.Cys2210Tyr variant has been reported in one individual with Marfan syndrome (Zhurayev 2016) and was absent from large population studies. Additionally, 4 other variants at the same position (p.Cys2210X, p.Cys2210Trp, p.Cys2210Ser, p.Cys2210Arg) have been identified in individual with features of Marfan syndrome (Lerner-Ellis 2014, ClinVar), suggesting that a change at this position may not be tolerated. Computational prediction tools and conservation analysis suggest that the p.Cys2210Tyr variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Furthermore, this variant affects a highly conserved cysteine residue in the EGF-like domains, which is a common finding in individuals with Marfan syndrome (Schrijver 1999). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Marfan syndrome. ACMG/AMP Criteria applied: PM1; PM2; PP3; PS4_Supporting.

#	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: May 7, 2024

ClinVar

Relating variation to medicine