Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207474 | SCV001378829 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2019-09-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys69*) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). This variant has not been reported in the literature in individuals with ACVRL1-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002418696 | SCV002725745 | pathogenic | Cardiovascular phenotype | 2017-01-23 | criteria provided, single submitter | clinical testing | The p.C69* pathogenic mutation (also known as c.207C>A), located in coding exon 2 of the ACVRL1 gene, results from a C to A substitution at nucleotide position 207. This changes the amino acid from a cysteine to a stop codon within coding exon 2. This mutation was identified in an individual with epistaxis, telangiectasias, arteriovenous malformations, and a family history of hereditary hemorrhagic telangiectasia (Richards-Yutz J et al. Hum. Genet., 2010 Jul;128:61-77). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |