ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.1445C>T (p.Ala482Val) (rs139142865)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766346 SCV000249625 uncertain significance not provided 2014-11-18 criteria provided, single submitter clinical testing p.Ala482Val (A482V) GCG>GTG: c.1445 C>T in exon 10 of the ACVRL1 gene (NM_000020.2). The A482V variant in the ACVRL1 gene has been reported in several unrelated individuals with HHT (Lesca G et al., 2004; Schulte C et al., 2005). However, additional publications report that the A482V variant is found in individuals with HHT when there is an additional disease causing mutation present (Letteboer T et al., 2005; McDonald J et al., 2009). Furthermore, functional studies show that the A482V variant does not alter protein function (Ricard N et al., 2010). In addition, the NHLBI Exome Sequencing Project reports A482V was observed in 25/8600 alleles (0.3%) from individuals of European ancestry, indicating it may be a rare benign variant in this population. Although this substitution occurs at a position that is highly conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function, the A482V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. A missense mutation in this residue (A482E) and missense mutations in nearby residues (L480F, R484W, R484G, R484L, R484Q) have been reported in association with HHT and PAH (Olivieri C et al., 2007), supporting the functional importance of this residue and region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in HHT-PANCARD,PAH-ARRHYTHMIA panel(s).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000196441 SCV000538228 likely benign not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Identified in multiple control cohorts; ExAC: 0.3% (190/66476) European chromosomes
Invitae RCV000470977 SCV000562552 likely benign Telangiectasia, hereditary hemorrhagic, type 2 2020-12-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000470977 SCV000602421 benign Telangiectasia, hereditary hemorrhagic, type 2 2020-04-14 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000470977 SCV000743470 benign Telangiectasia, hereditary hemorrhagic, type 2 2014-10-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000470977 SCV001272394 benign Telangiectasia, hereditary hemorrhagic, type 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
CSER _CC_NCGL, University of Washington RCV000148353 SCV000190043 likely benign Haemorrhagic telangiectasia 2 2014-06-01 no assertion criteria provided research
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000470977 SCV000745688 likely benign Telangiectasia, hereditary hemorrhagic, type 2 2016-11-09 no assertion criteria provided clinical testing
Birmingham Platelet Group; University of Birmingham RCV001270508 SCV001450807 uncertain significance Abnormal bleeding; Thrombocytopenia 2020-05-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.