Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410028 | SCV000485715 | likely pathogenic | Niemann-Pick disease, type C1 | 2016-02-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193401 | SCV001362190 | pathogenic | Niemann-Pick disease, type C | 2019-10-17 | criteria provided, single submitter | clinical testing | Variant summary: NPC1 c.395delC (p.Pro132LeufsX10) 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 251404 control chromosomes (gnomAD). c.395delC has been reported in the literature in individuals affected with Niemann-Pick Disease Type C (e.g. Sun_2001, Park_2003, Paciorkowski_2008, Garver_2010, Lo_2010). These data indicate that the variant is likely to be associated with disease. Fibroblasts from individuals with this variant showed markedly reduced levels of intracellular cholesterol esterification (e.g. Sun_2001, Lo_2010). A ClinVar submission (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000410028 | SCV003442433 | pathogenic | Niemann-Pick disease, type C1 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro132Leufs*10) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850). 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 disease type C (PMID: 11349231). This variant is also known as 394delC. ClinVar contains an entry for this variant (Variation ID: 370404). For these reasons, this variant has been classified as Pathogenic. |