ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2974G>A (p.Gly992Arg)

dbSNP: rs80358254
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000020229 SCV000220329 likely pathogenic Niemann-Pick disease, type C1 2014-05-19 criteria provided, single submitter literature only
GeneDx RCV000413372 SCV000491260 pathogenic not provided 2023-05-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19609713, 19307542, 26984608, 20301473, 26910362, 25665455, 31589614, 35892469, 11333381, 28710748, 25349751, 16126423)
Labcorp Genetics (formerly Invitae), Labcorp RCV000020229 SCV001391207 pathogenic Niemann-Pick disease, type C1 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 992 of the NPC1 protein (p.Gly992Arg). This variant is present in population databases (rs80358254, gnomAD 0.003%). This missense change has been observed in individuals with Niemann-Pick disease type C (PMID: 11333381, 20718790, 25349751, 26910362). ClinVar contains an entry for this variant (Variation ID: 21137). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NPC1 protein function with a positive predictive value of 95%. This variant disrupts the p.Gly992 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9634529, 16778374). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000020229 SCV002018350 pathogenic Niemann-Pick disease, type C1 2020-04-01 criteria provided, single submitter clinical testing
GeneReviews RCV000020229 SCV000040572 not provided Niemann-Pick disease, type C1 no assertion provided literature only
Natera, Inc. RCV000020229 SCV002095177 pathogenic Niemann-Pick disease, type C1 2020-09-25 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.