NM_000138.5(FBN1):c.3013G>A (p.Glu1005Lys) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 27, 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:: RCV001178815.4

Allele description [Variation Report for NM_000138.5(FBN1):c.3013G>A (p.Glu1005Lys)]

NM_000138.5(FBN1):c.3013G>A (p.Glu1005Lys)

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.3013G>A (p.Glu1005Lys)

Other names:

p.E1005K:GAG>AAG

HGVS:

NC_000015.10:g.48489920C>T
NG_008805.2:g.160869G>A
NM_000138.5:c.3013G>AMANE SELECT
NP_000129.3:p.Glu1005Lys
NP_000129.3:p.Glu1005Lys
LRG_778t1:c.3013G>A
LRG_778:g.160869G>A
LRG_778p1:p.Glu1005Lys
NC_000015.9:g.48782117C>T
NM_000138.4:c.3013G>A

Protein change:

E1005K

Links:

dbSNP: rs564713154

NCBI 1000 Genomes Browser:

rs564713154

Molecular consequence:

NM_000138.5:c.3013G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001343349	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 27, 2023)	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

SCV001343349

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 27, 2023)

germline

clinical testing

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

Help

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

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 Color Diagnostics, LLC DBA Color Health, SCV001343349.3

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

Description

This missense variant replaces glutamic acid with lysine at codon 1005 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/282862 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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