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NM_000138.5(FBN1):c.7643T>A (p.Phe2548Tyr) AND Marfan syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 1, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV003110180.3

Allele description [Variation Report for NM_000138.5(FBN1):c.7643T>A (p.Phe2548Tyr)]

NM_000138.5(FBN1):c.7643T>A (p.Phe2548Tyr)

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.7643T>A (p.Phe2548Tyr)
Other names:
NM_000138.5:c.7643T>A
HGVS:
  • NC_000015.10:g.48421614A>T
  • NG_008805.2:g.229175T>A
  • NM_000138.5:c.7643T>AMANE SELECT
  • NM_001406716.1:c.7643T>A
  • NP_000129.3:p.Phe2548Tyr
  • NP_000129.3:p.Phe2548Tyr
  • NP_001393645.1:p.Phe2548Tyr
  • LRG_778t1:c.7643T>A
  • LRG_778:g.229175T>A
  • LRG_778p1:p.Phe2548Tyr
  • NC_000015.9:g.48713811A>T
  • NM_000138.4:c.7643T>A
Protein change:
F2548Y
Molecular consequence:
  • NM_000138.5:c.7643T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406716.1:c.7643T>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

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003762204ClinGen FBN1 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(Assertion Criteria VCEP FBN1 Version 1)		Uncertain significance
(Dec 1, 2022) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen FBN1 Variant Curation Expert Panel, ClinGen, SCV003762204.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_00138 c.7643T>A is a missense variant predicted to cause a substitution of a phenylalanine by a tyrosine at amino acid position 2548. This variant is present in 1 proband with TAAD, segregating with TAAD in 1 affected family member but not segregating in another affected family member (BS4; Universitair Ziekenhuis Antwerpen). This variant occurs at a conserved position in the consensus calcium-binding sequence in a cbEGF-like domain (PM1). It is not present in gnomAD v2.1.1 (PM2_supporting). Computational prediction and evolutionary conservation analysis tools suggest no impact to the gene (BP4; REVEL = 0.298). Due to conflicting and insufficient evidence, this variant is classified as of uncertain significance for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PM1, PM2_supporting, BS4, BP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 11, 2023