NM_000138.5(FBN1):c.2956G>A (p.Ala986Thr) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Mar 16, 2018
Review status:: criteria provided, conflicting classifications

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:: RCV000143891.24

Allele description [Variation Report for NM_000138.5(FBN1):c.2956G>A (p.Ala986Thr)]

NM_000138.5(FBN1):c.2956G>A (p.Ala986Thr)

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.2956G>A (p.Ala986Thr)

Other names:

p.A986T:GCA>ACA; NM_000138.5(FBN1):c.2956G>A

HGVS:

NC_000015.10:g.48489977C>T
NG_008805.2:g.160812G>A
NM_000138.5:c.2956G>AMANE SELECT
NP_000129.3:p.Ala986Thr
NP_000129.3:p.Ala986Thr
LRG_778t1:c.2956G>A
LRG_778:g.160812G>A
LRG_778p1:p.Ala986Thr
NC_000015.9:g.48782174C>T
NM_000138.4:c.2956G>A
c.2956G>A

Protein change:

A986T

Links:

dbSNP: rs112287730

NCBI 1000 Genomes Browser:

rs112287730

Molecular consequence:

NM_000138.5:c.2956G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188760	Blueprint Genetics	no assertion criteria provided	Uncertain significance (Dec 27, 2013)	germline	clinical testing
SCV000317391	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Feb 18, 2015)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12402346, 19370756, 24793577 Citation Link,
SCV000392509	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV000902995	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Mar 16, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001333957	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Nov 16, 2017)	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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation screening of the fibrillin-1 (FBN1) gene in 76 unrelated patients with Marfan syndrome or Marfanoid features leads to the identification of 11 novel and three previously reported mutations.

Rommel K, Karck M, Haverich A, Schmidtke J, Arslan-Kirchner M.

Hum Mutat. 2002 Nov;20(5):406-7.

PubMed [citation]

PMID:: 12402346

UMD-predictor, a new prediction tool for nucleotide substitution pathogenicity -- application to four genes: FBN1, FBN2, TGFBR1, and TGFBR2.

Frédéric MY, Lalande M, Boileau C, Hamroun D, Claustres M, Béroud C, Collod-Béroud G.

Hum Mutat. 2009 Jun;30(6):952-9. doi: 10.1002/humu.20970.

PubMed [citation]

PMID:: 19370756

See all PubMed Citations (4)

Details of each submission

From Blueprint Genetics, SCV000188760.1

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

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

From Ambry Genetics, SCV000317391.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Illumina Laboratory Services, Illumina, SCV000392509.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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

From Color Diagnostics, LLC DBA Color Health, SCV000902995.1

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

#	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 CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001333957.1

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

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine