Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004572 | SCV001163656 | likely pathogenic | Niemann-Pick disease, type A | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307652 | SCV002600299 | likely pathogenic | Sphingomyelin/cholesterol lipidosis | 2022-10-05 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.107_116delinsCGC (p.Val36AlafsX39) 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 and several truncations have been associated with Niemann-Pick disease in HGMD. The variant was absent in 260806 control chromosomes (gnomAD). To our knowledge, no occurrence of c.107_116delinsCGC in individuals affected with Niemann-Pick Disease and no experimental evidence demonstrating its impact on protein function have 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 likely pathogenic. |
| Prevention |
RCV004743247 | SCV005366672 | pathogenic | SMPD1-related disorder | 2024-08-05 | no assertion criteria provided | clinical testing | The SMPD1 c.107_116delinsCGC variant is predicted to result in a frameshift and premature protein termination (p.Val36Alafs*39). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Frameshift variants in SMPD1 are expected to be pathogenic. This variant is interpreted as pathogenic. |