Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169205 | SCV000220458 | likely pathogenic | Niemann-Pick disease, type A | 2014-06-26 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169205 | SCV001431980 | pathogenic | Niemann-Pick disease, type A | 2020-08-31 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1111_1112delCT (p.Leu371PhefsX19) 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 249166 control chromosomes. c.1111_1112delCT has been reported in the literature in at-least one individual affected with Niemann-Pick Disease Type A and has been subsequently cited by others (example, Ricci_2004, Zampieri_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV003765054 | SCV004570130 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-03-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188853). This variant is also known as c.1110_1111delTC. This premature translational stop signal has been observed in individual(s) with clinical features of Niemann-Pick disease (PMID: 34554397). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu371Phefs*19) 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). |