Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001205003 | SCV001376238 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 2 | 2019-10-08 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual with clinical features of hereditary hemorrhagic telangiectasia (HHT) (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Lys487 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 14684682), which suggests that this may be a clinically significant amino acid residue. 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 and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 487 of the ACVRL1 protein (p.Lys487Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |