Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003768012 | SCV004588101 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-01-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln19Argfs*58) 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 not present in population databases (gnomAD no frequency). 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: 558404). For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV000674668 | SCV005086073 | pathogenic | Niemann-Pick disease, type A | 2023-12-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Niemann-Pick disease, type B, (MIM#607616), and Niemann-Pick disease, type A, (MIM#257200). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been reported once as likely pathogenic, and once as a VUS as part of a screening study (ClinVar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV003768012 | SCV005684489 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-05-23 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000674668 | SCV000800047 | likely pathogenic | Niemann-Pick disease, type A | 2018-05-18 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |