Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000003111 | SCV001140856 | pathogenic | Niemann-Pick disease, type C1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000003111 | SCV001586101 | pathogenic | Niemann-Pick disease, type C1 | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe1221Serfs*21) in the NPC1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the NPC1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Niemann-Pick type C (PMID: 11479732, 30820861). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2977). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002468957 | SCV002766003 | pathogenic | Niemann-Pick disease, type C | 2022-11-07 | criteria provided, single submitter | clinical testing | Variant summary: NPC1 c.3662delT (p.Phe1221SerfsX21) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251462 control chromosomes (gnomAD). c.3662delT has been reported in the literature in individuals affected with Niemann-Pick Disease Type C (examples: Polese-Bonatto_2019 and Ribeiro_2001). These data indicate that the variant is likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000003111 | SCV003807096 | pathogenic | Niemann-Pick disease, type C1 | 2023-02-03 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 strong, PM2 moderated, PM3 strong |
| OMIM | RCV000003111 | SCV000023269 | pathogenic | Niemann-Pick disease, type C1 | 2001-07-01 | no assertion criteria provided | literature only |