Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001032466 | SCV001195773 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2019-11-15 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 3-8 of the ACVRL1 gene. It preserves the integrity of the reading frame. This variant has been observed to segregate with hereditary haemorraghic telangiectasia (HHT) in a family (PMID: 23653583) and detected in an unrelated individuals with HHT (PMID: 16690726, 20414677). This variant affects a cysteine residue located within the ACVRL1 protein ectodomain. Cysteine residues in this domain of ACVRL1 are involved in the formation of disulfide bridges critical for protein structure and stability (PMID: 22028876, 22718755, 22799562). In addition, missense substitutions within the ACVRL1 ectodomain affecting cysteine residues are overrepresented in patients with HHT (PMID: 20501893, 26176610 and www.hhtmutation.org). For these reasons, this variant has been classified as Pathogenic. |