Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000688794 | SCV000816418 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2024-04-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala49Profs*5) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 12114496). ClinVar contains an entry for this variant (Variation ID: 568436). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002388215 | SCV002697148 | pathogenic | Cardiovascular phenotype | 2024-09-06 | criteria provided, single submitter | clinical testing | The c.145delG pathogenic mutation, located in coding exon 2 of the ACVRL1 gene, results from a deletion of one nucleotide at nucleotide position 145, causing a translational frameshift with a predicted alternate stop codon (p.A49Pfs*5). This pathogenic mutation was identified in an individual presenting with epistaxis and telangienctasias (Olivieri C, J. Med. Genet. 2002 Jul; 39(7):E39). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |