Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000412462 | SCV000486498 | likely pathogenic | Niemann-Pick disease, type C1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000412462 | SCV003443333 | pathogenic | Niemann-Pick disease, type C1 | 2024-06-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1189 of the NPC1 protein (p.Glu1189Gly). This variant is present in population databases (rs369098773, gnomAD 0.004%). This missense change has been observed in individual(s) with Niemann-Pick Type C (PMID: 11349231, 12205649, 26666848). ClinVar contains an entry for this variant (Variation ID: 371037). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004525924 | SCV005040017 | likely pathogenic | Niemann-Pick disease, type C | 2024-03-08 | criteria provided, single submitter | clinical testing | Variant summary: NPC1 c.3566A>G (p.Glu1189Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250986 control chromosomes. c.3566A>G has been reported in the literature in individuals affected with Niemann-Pick Disease Type C (Sun_2001, Saito_2004, Imrie_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 19744920, 26666848, 15099022, 11349231). ClinVar contains an entry for this variant (Variation ID: 371037). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genomics England Pilot Project, |
RCV000412462 | SCV001760423 | pathogenic | Niemann-Pick disease, type C1 | no assertion criteria provided | clinical testing |