Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001232672 | SCV001405238 | pathogenic | Niemann-Pick disease, type C1 | 2023-05-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NPC1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NPC1 protein in which other variant(s) (p.Leu1248Valfs*3) have been determined to be pathogenic (PMID: 10521290, 19744920). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 959341). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1226Leufs*16) in the NPC1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the NPC1 protein. |