Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002016966 | SCV002299935 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2021-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 164 of the SMPD1 protein (p.Gly164Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with acid sphingomyelinase deficiency (PMID: 30795770). 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. 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. |