Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001241647 | SCV001414678 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2019-10-02 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individuals affected with ASM deficiency (PMID: 23356216, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 382 of the SMPD1 protein (p.Leu382Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117860 | SCV003800815 | uncertain significance | not specified | 2023-01-21 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1144C>T (p.Leu382Phe) results in a non-conservative amino acid change located in the Calcineurin-like phosphoesterase domain (IPR004843) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249270 control chromosomes (gnomAD). c.1144C>T has been reported in the literature as a biallelic genotype in individuals affected with Niemann-Pick Disease (e.g. Zhang_2013, Dong_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV003462815 | SCV004205522 | likely pathogenic | Niemann-Pick disease, type A | 2023-01-27 | criteria provided, single submitter | clinical testing |