ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3634G>T (p.Val1212Leu) (rs753419933)

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
Counsyl RCV000675013 SCV000800439 likely pathogenic Niemann-Pick disease type C1 2018-06-06 criteria provided, single submitter clinical testing
Invitae RCV000675013 SCV001220112 likely pathogenic Niemann-Pick disease type C1 2019-03-05 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1212 of the NPC1 protein (p.Val1212Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs753419933, ExAC 0.02%). This variant has been observed to segregate with Niemann-Pick type C in a family and has also been observed in individuals affected with Niemann-Pick type C (PMID: 24915861, 22326530, 15774455, 22476655). ClinVar contains an entry for this variant (Variation ID: 558706). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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.