Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063146 | SCV001227980 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2019-03-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr374*) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with SMPD1-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005408670 | SCV006072344 | pathogenic | Niemann-Pick disease, type A | 2025-03-06 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1122C>G (p.Tyr374X) 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. The variant was absent in 249192 control chromosomes. To our knowledge, no occurrence of c.1122C>G in individuals affected with Niemann-Pick disease, type A and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 857473). Based on the evidence outlined above, the variant was classified as pathogenic. |