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NM_000020.3(ACVRL1):c.653G>C (p.Arg218Pro) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 14, 2016
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:
RCV000458880.7

Allele description [Variation Report for NM_000020.3(ACVRL1):c.653G>C (p.Arg218Pro)]

NM_000020.3(ACVRL1):c.653G>C (p.Arg218Pro)

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.653G>C (p.Arg218Pro)
HGVS:
  • NC_000012.12:g.51914466G>C
  • NG_009549.1:g.12049G>C
  • NM_000020.3:c.653G>CMANE SELECT
  • NM_001077401.2:c.653G>C
  • NP_000011.2:p.Arg218Pro
  • NP_000011.2:p.Arg218Pro
  • NP_001070869.1:p.Arg218Pro
  • LRG_543t1:c.653G>C
  • LRG_543:g.12049G>C
  • LRG_543p1:p.Arg218Pro
  • NC_000012.11:g.52308250G>C
  • NM_000020.2:c.653G>C
Protein change:
R218P
Links:
dbSNP: rs779287554
NCBI 1000 Genomes Browser:
rs779287554
Molecular consequence:
  • NM_000020.3:c.653G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.653G>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
SCV000552395Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 14, 2016) 		germlineclinical testing

PubMed (2)
[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

Clinical and genetic characteristics of Chinese patients with hereditary haemorrhagic telangiectasia-associated pulmonary hypertension.

Chen YJ, Yang QH, Liu D, Liu QQ, Eyries M, Wen L, Wu WH, Jiang X, Yuan P, Zhang R, Soubrier F, Jing ZC.

Eur J Clin Invest. 2013 Oct;43(10):1016-24. doi: 10.1111/eci.12138. Epub 2013 Aug 6.

PubMed [citation]
PMID:
23919827

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552395.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This sequence change replaces arginine with proline at codon 218 of the ACVRL1 protein (p.Arg218Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ACVRL1-related disease. A different variant (c.653_654delinsCC) giving rise to the same protein effect observed here (p.Arg218Pro) has been reported in two related individuals affected with hereditary haemorrhagic telangiectasia (PMID: 23919827), indicating that this residue may be critical for protein function. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024