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NM_000020.3(ACVRL1):c.866T>C (p.Leu289Pro) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 6, 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:
RCV003099999.3

Allele description [Variation Report for NM_000020.3(ACVRL1):c.866T>C (p.Leu289Pro)]

NM_000020.3(ACVRL1):c.866T>C (p.Leu289Pro)

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.866T>C (p.Leu289Pro)
HGVS:
  • NC_000012.12:g.51915318T>C
  • NG_009549.1:g.12901T>C
  • NM_000020.3:c.866T>CMANE SELECT
  • NM_001077401.2:c.866T>C
  • NM_001406487.1:c.866T>C
  • NM_001406488.1:c.866T>C
  • NM_001406489.1:c.866T>C
  • NM_001406490.1:c.554T>C
  • NM_001406491.1:c.554T>C
  • NM_001406492.1:c.554T>C
  • NM_001406493.1:c.554T>C
  • NM_001406494.1:c.554T>C
  • NM_001406495.1:c.302T>C
  • NP_000011.2:p.Leu289Pro
  • NP_000011.2:p.Leu289Pro
  • NP_001070869.1:p.Leu289Pro
  • NP_001393416.1:p.Leu289Pro
  • NP_001393417.1:p.Leu289Pro
  • NP_001393418.1:p.Leu289Pro
  • NP_001393419.1:p.Leu185Pro
  • NP_001393420.1:p.Leu185Pro
  • NP_001393421.1:p.Leu185Pro
  • NP_001393422.1:p.Leu185Pro
  • NP_001393423.1:p.Leu185Pro
  • NP_001393424.1:p.Leu101Pro
  • LRG_543t1:c.866T>C
  • LRG_543:g.12901T>C
  • LRG_543p1:p.Leu289Pro
  • NC_000012.11:g.52309102T>C
  • NM_000020.2:c.866T>C
Protein change:
L101P
Molecular consequence:
  • NM_000020.3:c.866T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.866T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406487.1:c.866T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406488.1:c.866T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406489.1:c.866T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406490.1:c.554T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406491.1:c.554T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406492.1:c.554T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406493.1:c.554T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406494.1:c.554T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406495.1:c.302T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Telangiectasia, hereditary hemorrhagic, type 2 (HHT2)
Synonyms:
Telangiectasia, hereditary hemorrhagic, type II; Osler Weber Rendu syndrome type 2
Identifiers:
MONDO: MONDO:0010880; MedGen: C1838163; Orphanet: 774; OMIM: 600376

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003441133Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 6, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype.

Bossler AD, Richards J, George C, Godmilow L, Ganguly A.

Hum Mutat. 2006 Jul;27(7):667-75.

PubMed [citation]
PMID:
16752392

Curaçao diagnostic criteria for hereditary hemorrhagic telangiectasia is highly predictive of a pathogenic variant in ENG or ACVRL1 (HHT1 and HHT2).

McDonald J, Bayrak-Toydemir P, DeMille D, Wooderchak-Donahue W, Whitehead K.

Genet Med. 2020 Jul;22(7):1201-1205. doi: 10.1038/s41436-020-0775-8. Epub 2020 Apr 17.

PubMed [citation]
PMID:
32300199
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441133.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACVRL1 protein function. ClinVar contains an entry for this variant (Variation ID: 1764244). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 16752392, 32300199). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 289 of the ACVRL1 protein (p.Leu289Pro).

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

Last Updated: Sep 29, 2024