ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3451G>A (p.Ala1151Thr) (rs765729815)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689227 SCV000816868 likely pathogenic Niemann-Pick disease type C1 2018-06-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1151 of the NPC1 protein (p.Ala1151Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs765729815, ExAC 0.007%). This variant has been observed in several individuals affected with Niemann-Pick disease Type C1 (PMID: 19744920, 27581084, 20718790, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000734932 SCV000863112 likely pathogenic not provided 2018-08-30 criteria provided, single submitter 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.