NM_000020.3(ACVRL1):c.1261T>G (p.Tyr421Asp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 10, 2017
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:: RCV002414359.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1261T>G (p.Tyr421Asp)]

NM_000020.3(ACVRL1):c.1261T>G (p.Tyr421Asp)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.1261T>G (p.Tyr421Asp)

HGVS:

NC_000012.12:g.51918999T>G
NG_009549.1:g.16582T>G
NM_000020.3:c.1261T>GMANE SELECT
NM_001077401.2:c.1261T>G
NM_001406487.1:c.1261T>G
NM_001406488.1:c.1261T>G
NM_001406489.1:c.1261T>G
NM_001406490.1:c.1105T>G
NM_001406491.1:c.949T>G
NM_001406492.1:c.949T>G
NM_001406493.1:c.949T>G
NM_001406494.1:c.751T>G
NM_001406495.1:c.697T>G
NP_000011.2:p.Tyr421Asp
NP_000011.2:p.Tyr421Asp
NP_001070869.1:p.Tyr421Asp
NP_001393416.1:p.Tyr421Asp
NP_001393417.1:p.Tyr421Asp
NP_001393418.1:p.Tyr421Asp
NP_001393419.1:p.Tyr369Asp
NP_001393420.1:p.Tyr317Asp
NP_001393421.1:p.Tyr317Asp
NP_001393422.1:p.Tyr317Asp
NP_001393423.1:p.Tyr251Asp
NP_001393424.1:p.Tyr233Asp
LRG_543t1:c.1261T>G
LRG_543:g.16582T>G
LRG_543p1:p.Tyr421Asp
NC_000012.11:g.52312783T>G
NM_000020.2:c.1261T>G

Protein change:

Y233D

Molecular consequence:

NM_000020.3:c.1261T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077401.2:c.1261T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406487.1:c.1261T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406488.1:c.1261T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406489.1:c.1261T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406490.1:c.1105T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406491.1:c.949T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406492.1:c.949T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406493.1:c.949T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406494.1:c.751T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406495.1:c.697T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002675889	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 10, 2017)	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

SCV002675889

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 10, 2017)

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

Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia.

Fontalba A, Fernandez-L A, García-Alegria E, Albiñana V, Garrido-Martin EM, Blanco FJ, Zarrabeitia R, Perez-Molino A, Bernabeu-Herrero ME, Ojeda ML, Fernandez-Luna JL, Bernabeu C, Botella LM.

BMC Med Genet. 2008 Aug 1;9:75. doi: 10.1186/1471-2350-9-75.

PubMed [citation]

PMID:: 18673552
PMCID:: PMC2518546

Details of each submission

From Ambry Genetics, SCV002675889.2

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

Description

The p.Y421D variant (also known as c.1261T>G), located in coding exon 8 of the ACVRL1 gene, results from a T to G substitution at nucleotide position 1261. The tyrosine at codon 421 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant was identified in 3 individuals from one family; all of the individuals presented with epistaxis and telangiectasias and one individual also had a pulmonary arteriovenous malformation (Fontalba A et al. BMC Med. Genet., 2008 Aug;9:75). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, 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: May 1, 2024

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