Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002971836 | SCV003287246 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 610 of the SMPD1 protein (p.Arg610Cys). This variant is present in population databases (rs375915127, gnomAD 0.03%). This missense change has been observed in individual(s) with acid sphingomyelinase deficiency (PMID: 34660203). ClinVar contains an entry for this variant (Variation ID: 2073371). 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%. 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. |
Revvity Omics, |
RCV003138419 | SCV003822021 | uncertain significance | not provided | 2021-10-25 | criteria provided, single submitter | clinical testing |