NM_000138.5(FBN1):c.5797G>A (p.Glu1933Lys) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 4, 2021
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:: RCV002036407.5

Allele description

NM_000138.5(FBN1):c.5797G>A (p.Glu1933Lys)

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.5797G>A (p.Glu1933Lys)

HGVS:

NC_000015.10:g.48445496C>T
NG_008805.2:g.205293G>A
NM_000138.4:c.5797G>A
NM_000138.5:c.5797G>AMANE SELECT
NP_000129.3:p.Glu1933Lys
LRG_778t1:c.5797G>A
LRG_778:g.205293G>A
NC_000015.9:g.48737693C>T

Protein change:

E1933K

Links:

dbSNP: rs2141249307

NCBI 1000 Genomes Browser:

rs2141249307

Molecular consequence:

NM_000138.5:c.5797G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

Recent activity

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H.sapiens TPRC gene
H.sapiens TPRC gene
gi|1869817|emb|X99720.1|

Nucleotide
SRX15152500 (1)
SRA
PREDICTED: Mus caroli olfactory receptor-like protein OLF3 (LOC110296968), mRNA
PREDICTED: Mus caroli olfactory receptor-like protein OLF3 (LOC110296968), mRNA
gi|1195726031|ref|XM_021165769.1|

Nucleotide
Uncharacterised protein [Klebsiella variicola]
Uncharacterised protein [Klebsiella variicola]
gi|1440166395|emb|STX60819.1||gnl|W MY|STX60819

Protein
anti-restriction protein [Klebsiella variicola]
anti-restriction protein [Klebsiella variicola]
gi|1440166381|emb|STX60805.1||gnl|W MY|STX60805

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002313262	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 4, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002313262

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 4, 2021)

germline

clinical testing

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

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002313262.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1933 of the FBN1 protein (p.Glu1933Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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

Last Updated: Mar 16, 2024

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