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NM_000138.5(FBN1):c.6890C>T (p.Thr2297Met) AND Marfan syndrome

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Dec 13, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000851302.7

Allele description [Variation Report for NM_000138.5(FBN1):c.6890C>T (p.Thr2297Met)]

NM_000138.5(FBN1):c.6890C>T (p.Thr2297Met)

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>T (p.Thr2297Met)
HGVS:
  • NC_000015.10:g.48428453G>A
  • NG_008805.2:g.222336C>T
  • NM_000138.5:c.6890C>TMANE SELECT
  • NP_000129.3:p.Thr2297Met
  • NP_000129.3:p.Thr2297Met
  • LRG_778t1:c.6890C>T
  • LRG_778:g.222336C>T
  • LRG_778p1:p.Thr2297Met
  • NC_000015.9:g.48720650G>A
  • NM_000138.4:c.6890C>T
Protein change:
T2297M
Links:
dbSNP: rs773785908
NCBI 1000 Genomes Browser:
rs773785908
Molecular consequence:
  • NM_000138.5:c.6890C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

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
SCV000993592HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - HudsonAlpha-AGHI-WGS
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Aug 30, 2018)
paternalresearch

PubMed (1)
[See all records that cite this PMID]

SCV001275271Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

Citation Link,

SCV004822418All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Dec 13, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown4not providednot provided108544not providedclinical testing
not providedpaternalunknown1not providednot provided1not providedresearch

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

Exome Sequencing Identifies Candidate Genetic Modifiers of Syndromic and Familial Thoracic Aortic Aneurysm Severity.

Landis BJ, Schubert JA, Lai D, Jegga AG, Shikany AR, Foroud T, Ware SM, Hinton RB.

J Cardiovasc Transl Res. 2017 Aug;10(4):423-432. doi: 10.1007/s12265-017-9753-1. Epub 2017 May 26.

PubMed [citation]
PMID:
28550590
PMCID:
PMC5702585
See all PubMed Citations (3)

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - HudsonAlpha-AGHI-WGS, SCV000993592.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalunknown1not providednot provided1not providednot providednot provided

From Illumina Laboratory Services, Illumina, SCV001275271.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From All of Us Research Program, National Institutes of Health, SCV004822418.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces threonine with methionine at codon 2297 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Marfan syndrome (PMID: 27112580, 28550590). This variant has been identified in 8/282666 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided4not providednot providednot provided

Last Updated: Sep 29, 2024