Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001388095 | SCV001588947 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2022-03-02 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1074702). This premature translational stop signal has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 16705692). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu337Argfs*17) 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). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002322371 | SCV002607845 | pathogenic | Cardiovascular phenotype | 2016-09-26 | criteria provided, single submitter | clinical testing | The c.1010delT pathogenic mutation, located in coding exon 6 of the ACVRL1 gene, results from a deletion of one nucleotide at nucleotide position 1010, causing a translational frameshift with a predicted alternate stop codon (p.L337Rfs*17). This mutation was detected in an individual with a clinical diagnosis of hereditary hemorrhagic telangiectasia (Lesca G et al. Hum. Mutat., 2006 Jun;27:598). It was also detected in an individual with epistaxis as well as cutaneous and gastrointestinal telangiectasias (McDonald J et al. Clin. Genet., 2011 Apr;79:335-44). 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. |