NM_000138.5(FBN1):c.5816G>A (p.Gly1939Glu) AND Marfan syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV004015281.2

Allele description [Variation Report for NM_000138.5(FBN1):c.5816G>A (p.Gly1939Glu)]

NM_000138.5(FBN1):c.5816G>A (p.Gly1939Glu)

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.5816G>A (p.Gly1939Glu)

HGVS:

NC_000015.10:g.48445477C>T
NG_008805.2:g.205312G>A
NM_000138.5:c.5816G>AMANE SELECT
NM_001406716.1:c.5816G>A
NP_000129.3:p.Gly1939Glu
NP_000129.3:p.Gly1939Glu
NP_001393645.1:p.Gly1939Glu
LRG_778t1:c.5816G>A
LRG_778:g.205312G>A
LRG_778p1:p.Gly1939Glu
NC_000015.9:g.48737674C>T
NM_000138.4:c.5816G>A

Protein change:

G1939E

Molecular consequence:

NM_000138.5:c.5816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406716.1:c.5816G>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

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Citrus reticulata cultivar:Ehime 38
Citrus reticulata cultivar:Ehime 38
Citrus reticulata cultivar:Ehime 38 Raw sequence reads

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004828116	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17627385, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004828116

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 28, 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	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Application of dHPLC for mutation detection of the fibrillin-1 gene for the diagnosis of Marfan syndrome in a National Health Service Laboratory.

Howarth R, Yearwood C, Harvey JF.

Genet Test. 2007 Summer;11(2):146-52.

PubMed [citation]

PMID:: 17627385

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, SCV004828116.1

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

Description

This missense variant replaces glycine with glutamic acid at codon 1939 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 suspected of having Marfan syndrome (PMID: 17627385). This variant has been identified in 2/250834 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		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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