Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672404 | SCV000797504 | pathogenic | Niemann-Pick disease, type C1 | 2018-01-30 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000729808 | SCV000857499 | pathogenic | not provided | 2017-10-11 | criteria provided, single submitter | clinical testing | |
| Centogene AG - |
RCV000672404 | SCV001426622 | pathogenic | Niemann-Pick disease, type C1 | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731877 | SCV001983445 | pathogenic | Niemann-Pick disease, type C | 2021-09-26 | criteria provided, single submitter | clinical testing | Variant summary: NPC1 c.1628delC (p.Pro543ArgfsX20) 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 251230 control chromosomes. c.1628delC has been reported in the literature as a compound heterozygous and homozygous genotype in individuals affected with Niemann-Pick Disease Type C (example, Sun_2001). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in complete absence of esterification of LDL-derived cholesterol in a homozygous patient derived cell line (example, Sun_2001). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000672404 | SCV004297806 | pathogenic | Niemann-Pick disease, type C1 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro543Argfs*20) 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, 28666962). ClinVar contains an entry for this variant (Variation ID: 556403). For these reasons, this variant has been classified as Pathogenic. |