Submissions for variant NM_001814.6(CTSC):c.503A>G (p.Tyr168Cys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005239952	SCV005887996	pathogenic	Papillon-Lefèvre syndrome	2025-01-29	criteria provided, single submitter	clinical testing	Variant summary: CTSC c.503A>G (p.Tyr168Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251230 control chromosomes. c.503A>G has been reported in the literature in multiple homozygous individuals affected with Papillon-Lefevre syndrome (Srensen_2014, Sanchez Klose_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in complete loss of protein expression in mature hematopoietic sutset of cells (Srensen_2014, Sanchez Klose_2021). The following publications have been ascertained in the context of this evaluation (PMID: 34932608, 25244098). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.