ClinVar Miner

Submissions for variant NM_000396.4(CTSK):c.436G>C (p.Gly146Arg)

gnomAD frequency: 0.00001  dbSNP: rs74315302
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623420 SCV000742962 pathogenic Inborn genetic diseases 2017-09-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001206530 SCV001377841 pathogenic not provided 2023-12-23 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 146 of the CTSK protein (p.Gly146Arg). This variant is present in population databases (rs74315302, gnomAD 0.01%). This missense change has been observed in individuals with pycnodysostosis (PMID: 8703060, 20044043, 27558267). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8421). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CTSK protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CTSK function (PMID: 10074491). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000008932 SCV002796189 pathogenic Pyknodysostosis 2022-01-19 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000008932 SCV004049728 pathogenic Pyknodysostosis 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000008932 SCV004215254 pathogenic Pyknodysostosis 2024-02-04 criteria provided, single submitter clinical testing
OMIM RCV000008932 SCV000029142 pathogenic Pyknodysostosis 1996-08-30 no assertion criteria provided literature only
Natera, Inc. RCV000008932 SCV002085806 pathogenic Pyknodysostosis 2020-07-21 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.