Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666408 | SCV000790695 | pathogenic | Niemann-Pick disease, type A | 2017-04-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269196 | SCV001448494 | pathogenic | Sphingomyelin/cholesterol lipidosis | 2020-11-23 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.84delC (p.Gly29AspfsX48) 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 allele was found at a frequency of 2e-05 in 244564 control chromosomes. c.84delC has been reported in the literature in individuals affected with Niemann-Pick Disease Type A (Sikora_2003, Irun_2013, Ordieres-Ortega_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001855459 | SCV002233254 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly29Aspfs*48) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801). This variant is present in population databases (rs750157176, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Neimann-Pick disease (PMID: 12556236, 23252888). ClinVar contains an entry for this variant (Variation ID: 551367). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000666408 | SCV004205535 | pathogenic | Niemann-Pick disease, type A | 2021-11-23 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000666408 | SCV002091652 | pathogenic | Niemann-Pick disease, type A | 2018-09-27 | no assertion criteria provided | clinical testing |