Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693390 | SCV000821258 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 70 of the ACVRL1 protein (p.Gly70Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 21158752; Invitae). ClinVar contains an entry for this variant (Variation ID: 572085). 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 80%. For these reasons, this variant has been classified as Pathogenic. |
Mayo Clinic Laboratories, |
RCV001507803 | SCV001713596 | uncertain significance | not provided | 2019-11-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002422508 | SCV002731055 | uncertain significance | Cardiovascular phenotype | 2017-08-08 | criteria provided, single submitter | clinical testing | The p.G70R variant (also known as c.208G>A), located in coding exon 2 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 208. The glycine at codon 70 is replaced by arginine, an amino acid with dissimilar properties. This variant was detected in an individual with epistaxis, pulmonary arteriovenous malformations, and a family history (McDonald J et al. Clin. Genet., 2011 Apr;79:335-44). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this variant remains unclear. |