U.S. flag

An official website of the United States government

NM_000138.5(FBN1):c.6534T>A (p.Asn2178Lys) AND Marfan syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 23, 2024
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:
RCV004002729.3

Allele description [Variation Report for NM_000138.5(FBN1):c.6534T>A (p.Asn2178Lys)]

NM_000138.5(FBN1):c.6534T>A (p.Asn2178Lys)

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.6534T>A (p.Asn2178Lys)
HGVS:
  • NC_000015.10:g.48434676A>T
  • NG_008805.2:g.216113T>A
  • NM_000138.5:c.6534T>AMANE SELECT
  • NP_000129.3:p.Asn2178Lys
  • NP_000129.3:p.Asn2178Lys
  • LRG_778t1:c.6534T>A
  • LRG_778:g.216113T>A
  • LRG_778p1:p.Asn2178Lys
  • NC_000015.9:g.48726873A>T
  • NM_000138.4:c.6534T>A
Protein change:
N2178K
Links:
dbSNP: rs770257902
NCBI 1000 Genomes Browser:
rs770257902
Molecular consequence:
  • NM_000138.5:c.6534T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
5

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

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
SCV004822441All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Sep 23, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown5not providednot provided143475not providedclinical testing

Citations

PubMed

Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis.

Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, Willing MC, Grange DK, Braverman AC, Miller NH, Morcuende JA, Tang NL, Lam TP, Ng BK, Cheng JC, Dobbs MB, Gurnett CA.

Hum Mol Genet. 2014 Oct 1;23(19):5271-82. doi: 10.1093/hmg/ddu224. Epub 2014 May 15.

PubMed [citation]
PMID:
24833718
PMCID:
PMC4159151

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004822441.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces asparagine with lysine at codon 2178 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 one individual who was affected with adolescent idiopathic scoliosis but did not meet criteria for Marfan syndrome diagnosis (PMID: 24833718). This variant has been identified in 3/282550 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
1germlineunknown143475not providednot provided5not providednot providednot provided

Last Updated: Jan 13, 2025