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NM_000020.3(ACVRL1):c.940C>T (p.His314Tyr) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 12, 2020
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:
RCV002369971.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.940C>T (p.His314Tyr)]

NM_000020.3(ACVRL1):c.940C>T (p.His314Tyr)

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.940C>T (p.His314Tyr)
HGVS:
  • NC_000012.12:g.51915392C>T
  • NG_009549.1:g.12975C>T
  • NM_000020.3:c.940C>TMANE SELECT
  • NM_001077401.2:c.940C>T
  • NP_000011.2:p.His314Tyr
  • NP_000011.2:p.His314Tyr
  • NP_001070869.1:p.His314Tyr
  • LRG_543t1:c.940C>T
  • LRG_543:g.12975C>T
  • LRG_543p1:p.His314Tyr
  • NC_000012.11:g.52309176C>T
  • NM_000020.2:c.940C>T
Protein change:
H314Y
Links:
dbSNP: rs1565594311
NCBI 1000 Genomes Browser:
rs1565594311
Molecular consequence:
  • NM_000020.3:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002683795Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 12, 2020) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.

Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Rivière S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S; French Rendu-Osler Network..

Hum Mutat. 2004 Apr;23(4):289-99.

PubMed [citation]
PMID:
15024723

High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients.

Schulte C, Geisthoff U, Lux A, Kupka S, Zenner HP, Blin N, Pfister M.

Hum Mutat. 2005 Jun;25(6):595.

PubMed [citation]
PMID:
15880681
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002683795.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.H314Y pathogenic mutation (also known as c.940C>T), located in coding exon 6 of the ACVRL1 gene, results from a C to T substitution at nucleotide position 940. The histidine at codon 314 is replaced by tyrosine, an amino acid with similar properties. This alteration have been reported in multiple individuals with confirmed or suspected hereditary hemorrhagic telangiectasia (Lesca G et al. Hum Mutat, 2004 Apr;23:289-99; Prigoda NL et al. J Med Genet, 2006 Sep;43:722-8; Schulte C et al. Hum Mutat, 2005 Jun;25:595; Seo J et al. Ann Dermatol, 2016 Apr;28:264-6). Based on internal structural analysis, H314Y disrupts the structure of the C-lobe of the kinase domain of ACVRL1 (Kerr G et al. Angiogenesis, 2015 Apr;18:209-17). Functional analyses showed that the H314Y mutation results in a maturation defect and that mutant protein fails to reach the cell surface; additionally, although mutant protein was able to respond to BMP9 stimulation to some extent, it was substantially lower as compared to wild type (Alaa El Din F et al. PLoS One, 2015 Jul;10:e0132111). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024