ClinVar Miner

Submissions for variant NM_000396.4(CTSK):c.121-1G>A

gnomAD frequency: 0.00001  dbSNP: rs587663163
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065547 SCV001230508 pathogenic not provided 2024-02-23 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the CTSK gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs587663163, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with pycnodysostosis (PMID: 10878663). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 859435). Studies have shown that disruption of this splice site results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 10878663). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003467829 SCV004215242 pathogenic Pyknodysostosis 2023-09-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003467829 SCV005671336 likely pathogenic Pyknodysostosis 2024-03-31 criteria provided, single submitter clinical testing

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