Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001064308 | SCV001229201 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2019-10-03 | criteria provided, single submitter | clinical testing | This variant disrupts the p.His314 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15024723, 15880681, 16690726, 26176610). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 (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 has been observed in an individual with hereditary hemorrhagic telangiectasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with asparagine at codon 314 of the ACVRL1 protein (p.His314Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine. |