Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001063288 | SCV001228126 | pathogenic | Sphingolipid activator protein 1 deficiency | 2023-09-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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 PSAP protein function. ClinVar contains an entry for this variant (Variation ID: 857581). This missense change has been observed in individual(s) with atypical metachromatic leukodystrophy due to saposin B deficiency (PMID: 10196694, 17616409, 18693274, 26462614). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770171865, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 215 of the PSAP protein (p.Asn215Lys). |
Natera, |
RCV001827403 | SCV002087042 | likely pathogenic | Metachromatic leukodystrophy | 2020-08-15 | no assertion criteria provided | clinical testing |