ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1214C>T (p.Thr405Met)

gnomAD frequency: 0.00001  dbSNP: rs764364312
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000734940 SCV000863120 uncertain significance not provided 2018-08-27 criteria provided, single submitter clinical testing
Invitae RCV001869000 SCV002300707 uncertain significance Niemann-Pick disease, type C1 2022-06-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 405 of the NPC1 protein (p.Thr405Met). This variant is present in population databases (rs764364312, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NPC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 598529). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002352255 SCV002655182 uncertain significance Inborn genetic diseases 2021-11-29 criteria provided, single submitter clinical testing The p.T405M variant (also known as c.1214C>T), located in coding exon 8 of the NPC1 gene, results from a C to T substitution at nucleotide position 1214. The threonine at codon 405 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.