NM_000138.5(FBN1):c.8081G>A (p.Arg2694Gln) AND Marfan syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 11, 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:: RCV000148495.4

Allele description [Variation Report for NM_000138.5(FBN1):c.8081G>A (p.Arg2694Gln)]

NM_000138.5(FBN1):c.8081G>A (p.Arg2694Gln)

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.8081G>A (p.Arg2694Gln)

HGVS:

NC_000015.10:g.48412714C>T
NG_008805.2:g.238075G>A
NM_000138.5:c.8081G>AMANE SELECT
NP_000129.3:p.Arg2694Gln
NP_000129.3:p.Arg2694Gln
LRG_778t1:c.8081G>A
LRG_778:g.238075G>A
LRG_778p1:p.Arg2694Gln
NC_000015.9:g.48704911C>T
NM_000138.4:c.8081G>A

Protein change:

R2694Q

Links:

dbSNP: rs371375126

NCBI 1000 Genomes Browser:

rs371375126

Molecular consequence:

NM_000138.5:c.8081G>A - 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

Recent activity

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glutathione S-transferase P [Rattus norvegicus]
glutathione S-transferase P [Rattus norvegicus]
gi|25453420|ref|NP_036709.1|

Protein
MALT1 (534)
PubChem BioAssay
peroxiredoxin-6 [Sus scrofa]
peroxiredoxin-6 [Sus scrofa]
gi|47523870|ref|NP_999573.1|

Protein
PRJNA812855 (47)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000190202	CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation	no assertion criteria provided	Uncertain significance (Jun 1, 2014)	germline	research
SCV004844925	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19839986, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000190202

CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation

no assertion criteria provided

Uncertain significance
(Jun 1, 2014)

germline

research

SCV004844925

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 11, 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	7	not provided	not provided	108544	not provided	clinical testing, research

Citations

PubMed

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome.

Hung CC, Lin SY, Lee CN, Cheng HY, Lin SP, Chen MR, Chen CP, Chang CH, Lin CY, Yu CC, Chiu HH, Cheng WF, Ho HN, Niu DM, Su YN.

Ann Hum Genet. 2009 Nov;73(Pt 6):559-67. doi: 10.1111/j.1469-1809.2009.00545.x.

PubMed [citation]

PMID:: 19839986

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 CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation, SCV000190202.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

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

From All of Us Research Program, National Institutes of Health, SCV004844925.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces arginine with glutamine at codon 2694 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with suspected Marfan Syndrome (PMID: 19839986). This variant has been identified in 1/251390 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		7	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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