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NM_000138.5(FBN1):c.8363C>T (p.Thr2788Met) AND Marfan syndrome

Germline classification:
Benign (3 submissions)
Last evaluated:
Feb 1, 2023
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:
RCV000279195.15

Allele description [Variation Report for NM_000138.5(FBN1):c.8363C>T (p.Thr2788Met)]

NM_000138.5(FBN1):c.8363C>T (p.Thr2788Met)

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.8363C>T (p.Thr2788Met)
Other names:
NM_000138.4(FBN1):c.8363C>T; p.Thr2788Met
HGVS:
  • NC_000015.10:g.48411243G>A
  • NG_008805.2:g.239546C>T
  • NM_000138.5:c.8363C>TMANE SELECT
  • NP_000129.3:p.Thr2788Met
  • NP_000129.3:p.Thr2788Met
  • LRG_778t1:c.8363C>T
  • LRG_778:g.239546C>T
  • LRG_778p1:p.Thr2788Met
  • NC_000015.9:g.48703440G>A
  • NM_000138.4:c.8363C>T
Protein change:
T2788M
Links:
dbSNP: rs143007898
NCBI 1000 Genomes Browser:
rs143007898
Molecular consequence:
  • NM_000138.5:c.8363C>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000392039Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification 20161018)
Likely benign
(Jun 14, 2016)
germlineclinical testing

ICSL_Variant_Classification_20161018.pdf,

Citation Link,

SCV000787410Center for Medical Genetics Ghent, University of Ghent
no assertion criteria provided
Likely benign
(Nov 7, 2017)
germlineclinical testing

SCV003762195ClinGen FBN1 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(Assertion Criteria VCEP FBN1 Version 1)
Benign
(Feb 1, 2023)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000392039.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Medical Genetics Ghent, University of Ghent, SCV000787410.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From ClinGen FBN1 Variant Curation Expert Panel, ClinGen, SCV003762195.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_00138 c.8363C>T, is a missense variant in FBN1 predicted to cause a substitution of a threonine by methionine at amino acid 2788 (p.Thr2788Met). The variant in FBN1 has been reported 13 times in ClinVar: 12 times as likely benign and once as benign (Variation ID: 263832). This variant has been identified in 44 individuals of African origin (gnomAD version 3.1.1, MAF: 0.1%, one homozygous) (BA1; https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analysis are unclear on the predicted impact on the protein (REVEL: 0.356). The constraint z-score for missense variants affecting FBN1 is 5.06, however due to the presence of benign arguments PP2 cannot be used. In summary, this variant meets criteria to be classified as benign for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: BA1.

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

Last Updated: Oct 26, 2024