U.S. flag

An official website of the United States government

NM_000138.5(FBN1):c.6890C>G (p.Thr2297Arg) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 28, 2022
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:
RCV002876000.3

Allele description [Variation Report for NM_000138.5(FBN1):c.6890C>G (p.Thr2297Arg)]

NM_000138.5(FBN1):c.6890C>G (p.Thr2297Arg)

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.6890C>G (p.Thr2297Arg)
HGVS:
  • NC_000015.10:g.48428453G>C
  • NG_008805.2:g.222336C>G
  • NM_000138.5:c.6890C>GMANE SELECT
  • NM_001406716.1:c.6890C>G
  • NP_000129.3:p.Thr2297Arg
  • NP_000129.3:p.Thr2297Arg
  • NP_001393645.1:p.Thr2297Arg
  • LRG_778t1:c.6890C>G
  • LRG_778:g.222336C>G
  • LRG_778p1:p.Thr2297Arg
  • NC_000015.9:g.48720650G>C
  • NM_000138.4:c.6890C>G
Protein change:
T2297R
Molecular consequence:
  • NM_000138.5:c.6890C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406716.1:c.6890C>G - 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
SCV003225074Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 28, 2022) 		germlineclinical testing

PubMed (2)
[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

Analysis of TGFBR1*6A variant in individuals evaluated for Marfan syndrome.

Somers AE, Hinton RB, Pilipenko V, Miller E, Ware SM.

Am J Med Genet A. 2016 Jul;170(7):1786-90. doi: 10.1002/ajmg.a.37668. Epub 2016 Apr 26.

PubMed [citation]
PMID:
27112580

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003225074.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 2297 of the FBN1 protein (p.Thr2297Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Thr2297 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27112580; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with clinical features of Marfan syndrome (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.0009%).

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

Last Updated: Sep 29, 2024