Submissions for variant NM_000396.4(CTSK):c.236G>A (p.Gly79Glu)

dbSNP: rs74315305

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000008935	SCV004215245	pathogenic	Pyknodysostosis	2023-08-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000008935	SCV005077009	pathogenic	Pyknodysostosis	2024-04-23	criteria provided, single submitter	clinical testing	Variant summary: CTSK c.236G>A (p.Gly79Glu) results in a non-conservative amino acid change located in the Cathepsin propeptide inhibitor domain (IPR013201) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251314 control chromosomes. c.236G>A has been reported in the literature in individuals affected with Pyknodysostosis (examples: Haagerup_2000, Ho_1999, Hou_1999, Sait_2021). These data indicate that the variant is likely to be associated with disease. Multiple publications report experimental evidence evaluating an impact on protein function (Hou_1999, Roy_2018). The most pronounced variant effect results in the absence of protease activity. The following publications have been ascertained in the context of this evaluation (PMID: 10878663, 10491211, 10074491, 30199612, 33945887). ClinVar contains an entry for this variant (Variation ID: 8424). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM	RCV000008935	SCV000029145	pathogenic	Pyknodysostosis	1999-10-01	no assertion criteria provided	literature only