Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668933 | SCV000793613 | uncertain significance | Niemann-Pick disease, type C1 | 2017-08-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000668933 | SCV003442632 | likely pathogenic | Niemann-Pick disease, type C1 | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 386 of the NPC1 protein (p.Ser386Gly). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with Niemann-Pick type C (PMID: 27528516). ClinVar contains an entry for this variant (Variation ID: 553470). 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 NPC1 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. |