Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000812276 | SCV000952585 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2019-01-22 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Asp397 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 15024723, Invitae), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class 15"). This sequence change replaces aspartic acid with asparagine at codon 397 of the ACVRL1 protein (p.Asp397Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals affected with hereditary hemorrhagic telangiectasia (PMID: 15517393, 16690726, Invitae). |