ClinVar Miner

Submissions for variant NM_000396.4(CTSK):c.721C>T (p.Arg241Ter)

dbSNP: rs74315303
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000008933 SCV000220929 likely pathogenic Pyknodysostosis 2014-12-02 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV001036147 SCV001199497 pathogenic not provided 2023-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg241*) in the CTSK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTSK are known to be pathogenic (PMID: 12125807, 21569238). This variant is present in population databases (rs74315303, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with pycnodysostosis (PMID: 8703060, 8938428). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8422). For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000008933 SCV003807164 pathogenic Pyknodysostosis 2022-08-12 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 supporting, PM3 very strong, PP1 strong
Genome-Nilou Lab RCV000008933 SCV004049719 likely pathogenic Pyknodysostosis 2023-04-11 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000008933 SCV004100633 pathogenic Pyknodysostosis criteria provided, single submitter clinical testing The stop gained p.R241* in CTSK (NM_000396.4) has been observed in individuals affected with pycnodysostosis, and has been shown to segregate with disease in a family (B D Gelb et al; M R Johnson). It is expected to result in an absent or disrupted protein product. The variant has been reported to ClinVar as Pathogenic/Likely Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000008933 SCV004215238 pathogenic Pyknodysostosis 2023-11-28 criteria provided, single submitter clinical testing
OMIM RCV000008933 SCV000029143 pathogenic Pyknodysostosis 1996-11-01 no assertion criteria provided literature only
Natera, Inc. RCV000008933 SCV001461731 pathogenic Pyknodysostosis 2020-09-16 no assertion criteria provided clinical testing

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