U.S. flag

An official website of the United States government

NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 10, 2023
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:
RCV000689140.7

Allele description [Variation Report for NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro)]

NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro)

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.1900T>C (p.Ser634Pro)
HGVS:
  • NC_000015.10:g.48505085A>G
  • NG_008805.2:g.145704T>C
  • NM_000138.5:c.1900T>CMANE SELECT
  • NP_000129.3:p.Ser634Pro
  • NP_000129.3:p.Ser634Pro
  • LRG_778t1:c.1900T>C
  • LRG_778:g.145704T>C
  • LRG_778p1:p.Ser634Pro
  • NC_000015.9:g.48797282A>G
  • NM_000138.4:c.1900T>C
Protein change:
S634P
Links:
dbSNP: rs1566914005
NCBI 1000 Genomes Browser:
rs1566914005
Molecular consequence:
  • NM_000138.5:c.1900T>C - 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
Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000816780Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 10, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Role of ADAMTSL4 mutations in FBN1 mutation-negative ectopia lentis patients.

Aragon-Martin JA, Ahnood D, Charteris DG, Saggar A, Nischal KK, Comeglio P, Chandra A, Child AH, Arno G.

Hum Mutat. 2010 Aug;31(8):E1622-31. doi: 10.1002/humu.21305.

PubMed [citation]
PMID:
20564469

Relation between genotype and left-ventricular dilatation in patients with Marfan syndrome.

Aalberts JJ, van Tintelen JP, Meijboom LJ, Polko A, Jongbloed JD, van der Wal H, Pals G, Osinga J, Timmermans J, de Backer J, Bakker MK, van Veldhuisen DJ, Hofstra RM, Mulder BJ, van den Berg MP.

Gene. 2014 Jan 15;534(1):40-3. doi: 10.1016/j.gene.2013.10.033. Epub 2013 Oct 24.

PubMed [citation]
PMID:
24161884
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000816780.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 568701). This missense change has been observed in individuals with ectopia lentis and Marfan syndrome (PMID: 20564469, 24161884; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 634 of the FBN1 protein (p.Ser634Pro).

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

Last Updated: Mar 5, 2024