Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001071343 | SCV001236640 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2022-08-09 | 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 SMPD1 protein function. ClinVar contains an entry for this variant (Variation ID: 864212). This variant is also known as g.3337T > C (F463S). This missense change has been observed in individual(s) with Niemann-Pick disease (PMID: 12556236, 22818240, 27338287, 33675270). 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 (no rsID available, gnomAD 0.0009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 465 of the SMPD1 protein (p.Phe465Ser). |
Diagnostics Division, |
RCV001527428 | SCV001738431 | likely pathogenic | Niemann-Pick disease, type A | 2021-04-25 | criteria provided, single submitter | research | |
Baylor Genetics | RCV001527428 | SCV005052835 | pathogenic | Niemann-Pick disease, type A | 2024-03-30 | criteria provided, single submitter | clinical testing |