Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000805997 | SCV000945975 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-02-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu352*) 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 (rs201550531, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 650777). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001004583 | SCV001163673 | pathogenic | Niemann-Pick disease, type A | 2024-01-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269099 | SCV001448340 | likely pathogenic | Sphingomyelin/cholesterol lipidosis | 2023-02-07 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1054G>T (p.Glu352X) 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 1.6e-05 in 251074 control chromosomes. c.1054G>T has been reported in the literature in one individual who may have atherosclerosis (Johnston_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three 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 likely pathogenic. |
| Revvity Omics, |
RCV001784429 | SCV002020759 | pathogenic | not provided | 2020-12-03 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000805997 | SCV002796210 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-06-07 | criteria provided, single submitter | clinical testing |