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NM_000020.3(ACVRL1):c.1007T>A (p.Val336Glu) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 14, 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:
RCV000696651.7

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1007T>A (p.Val336Glu)]

NM_000020.3(ACVRL1):c.1007T>A (p.Val336Glu)

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.1007T>A (p.Val336Glu)
HGVS:
  • NC_000012.12:g.51915459T>A
  • NG_009549.1:g.13042T>A
  • NM_000020.3:c.1007T>AMANE SELECT
  • NM_001077401.2:c.1007T>A
  • NP_000011.2:p.Val336Glu
  • NP_000011.2:p.Val336Glu
  • NP_001070869.1:p.Val336Glu
  • LRG_543t1:c.1007T>A
  • LRG_543:g.13042T>A
  • LRG_543p1:p.Val336Glu
  • NC_000012.11:g.52309243T>A
  • NM_000020.2:c.1007T>A
Protein change:
V336E
Links:
dbSNP: rs1565594467
NCBI 1000 Genomes Browser:
rs1565594467
Molecular consequence:
  • NM_000020.3:c.1007T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1007T>A - 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
SCV000825220Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 14, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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, SCV000825220.4

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

Description

This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 336 of the ACVRL1 protein (p.Val336Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 574660). 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 with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024