ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2800C>T (p.Arg934Ter)

gnomAD frequency: 0.00001  dbSNP: rs370721218
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174732 SCV001338021 pathogenic Niemann-Pick disease, type C 2020-01-06 criteria provided, single submitter clinical testing Variant summary: NPC1 c.2800C>T (p.Arg934X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 248426 control chromosomes (gnomAD). c.2800C>T has been reported in the literature in multiple individuals affected with Niemann-Pick Disease Type C (e.g. Fancello_2009, Heron_2012). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001383764 SCV001583025 pathogenic Niemann-Pick disease, type C1 2023-05-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 917636). This premature translational stop signal has been observed in individuals with Niemann-Pick Type C (PMID: 19252935, 27599728, 32138288). This variant is present in population databases (rs370721218, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg934*) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850).
GeneDx RCV001570592 SCV001794911 pathogenic not provided 2021-05-12 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27599728, 32138288, 22676771, 32709131, 20554533, 26790753, 27193329, 21344635, 19252935, 25525159)
Mayo Clinic Laboratories, Mayo Clinic RCV001570592 SCV005413285 pathogenic not provided 2024-03-20 criteria provided, single submitter clinical testing PP4, PM2, PM3, PVS1
Natera, Inc. RCV001383764 SCV002095181 pathogenic Niemann-Pick disease, type C1 2020-06-26 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.