Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000548777 | SCV000407866 | uncertain significance | Niemann-Pick disease, type C1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000548777 | SCV000650838 | pathogenic | Niemann-Pick disease, type C1 | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 757 of the NPC1 protein (p.Val757Met). This variant is present in population databases (rs777156729, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of Niemann-Pick Type C disease (PMID: 30285904; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 326264). 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%. For these reasons, this variant has been classified as Pathogenic. |
| Eurofins Ntd Llc |
RCV000594494 | SCV000703020 | uncertain significance | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000548777 | SCV001455865 | uncertain significance | Niemann-Pick disease, type C1 | 2020-09-16 | no assertion criteria provided | clinical testing |