Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000178790 | SCV000230946 | uncertain significance | not provided | 2014-10-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002516782 | SCV003439567 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2022-09-13 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMPD1 protein function. ClinVar contains an entry for this variant (Variation ID: 197685). This missense change has been observed in individual(s) with Niemann-Pick disease (PMID: 24643943). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 460 of the SMPD1 protein (p.Thr460Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387789 | SCV004099835 | uncertain significance | not specified | 2023-09-14 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1378A>C (p.Thr460Pro) results in a non-conservative amino acid change located in the metallophosphoesterase catalytic domain (Grasko_2014) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251492 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1378A>C has been reported in the literature in the compound heterozygous state in an individual affected with Niemann-Pick Disease (Grasko_2014). Altogether these data suggest the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24643943). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |