Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001390955 | SCV001592862 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 280 of the SMPD1 protein (p.Asp280Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Niemann-Pick disease (PMID: 15877209). It has also been observed to segregate with disease in related individuals. This variant is also known as D278A. ClinVar contains an entry for this variant (Variation ID: 1076908). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SMPD1 function (PMID: 15877209). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001831407 | SCV005052850 | pathogenic | Niemann-Pick disease, type A | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001831407 | SCV002092249 | pathogenic | Niemann-Pick disease, type A | 2017-03-17 | no assertion criteria provided | clinical testing |