NM_000138.5(FBN1):c.3766A>G (p.Asn1256Asp) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 14, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001180697.5

Allele description [Variation Report for NM_000138.5(FBN1):c.3766A>G (p.Asn1256Asp)]

NM_000138.5(FBN1):c.3766A>G (p.Asn1256Asp)

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.3766A>G (p.Asn1256Asp)

HGVS:

NC_000015.10:g.48483890T>C
NG_008805.2:g.166899A>G
NM_000138.5:c.3766A>GMANE SELECT
NP_000129.3:p.Asn1256Asp
LRG_778t1:c.3766A>G
LRG_778:g.166899A>G
NC_000015.9:g.48776087T>C
NC_000015.9:g.48776087T>C
NM_000138.4:c.3766A>G

Protein change:

N1256D

Links:

dbSNP: rs772890884

NCBI 1000 Genomes Browser:

rs772890884

Molecular consequence:

NM_000138.5:c.3766A>G - 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
SCV001345693	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 11, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002619737	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001345693

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 11, 2019)

germline

clinical testing

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

SCV002619737

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 14, 2019)

germline

clinical testing

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

Citation Link

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

The phenotypic heterogeneity of patients with Marfan-related disorders and their variant spectrums.

Seo GH, Kim YM, Kang E, Kim GH, Seo EJ, Lee BH, Choi JH, Yoo HW.

Medicine (Baltimore). 2018 May;97(20):e10767. doi: 10.1097/MD.0000000000010767.

PubMed [citation]

PMID:: 29768367
PMCID:: PMC5976283

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001345693.2

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

Description

Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces asparagine with aspartic acid at codon 1256 of the FBN1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/245904 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.

#	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 Ambry Genetics, SCV002619737.2

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

Description

The p.N1256D variant (also known as c.3766A>G), located in coding exon 30 of the FBN1 gene, results from an A to G substitution at nucleotide position 3766. The asparagine at codon 1256 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was reported in an individual with Marfan-like features; however, clinical details were limited (Seo GH et al. Medicine (Baltimore), 2018 May;97:e10767). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

ClinVar

Relating variation to medicine