NM_000138.5(FBN1):c.2090A>G (p.Gln697Arg) AND Marfan syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 15, 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:: RCV004008272.2

Allele description [Variation Report for NM_000138.5(FBN1):c.2090A>G (p.Gln697Arg)]

NM_000138.5(FBN1):c.2090A>G (p.Gln697Arg)

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.2090A>G (p.Gln697Arg)

HGVS:

NC_000015.10:g.48503810T>C
NG_008805.2:g.146979A>G
NM_000138.5:c.2090A>GMANE SELECT
NP_000129.3:p.Gln697Arg
LRG_778t1:c.2090A>G
LRG_778:g.146979A>G
NC_000015.9:g.48796007T>C
NM_000138.4:c.2090A>G

Protein change:

Q697R

Links:

dbSNP: rs769708437

NCBI 1000 Genomes Browser:

rs769708437

Molecular consequence:

NM_000138.5:c.2090A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004814923	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24833718, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004814923

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 15, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	4	not provided	not provided	108544	not provided	clinical 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, SCV004814923.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (2)

Description

Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the TGFbeta-like motif 3 of the FBN1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with adolescent idiopathic scoliosis (PMID: 24833718). This variant has been identified in 1/246152 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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