Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000708277 | SCV000837387 | pathogenic | Familial hypercholesterolemia | 2019-06-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 15-18 of the LDLR gene. The 5' boundary is likely confined to intron 14. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has been observed in several individuals affected with hypercholesterolemia (PMID: 16250003, 1319734, 24075752, 17142622, Invitae). This variant disrupts the p.Val797Met amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7649549, 23375686, 19446849, 22698793, 22859806, 20145306, 9763532). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |