ClinVar Miner

Submissions for variant NM_001814.6(CTSC):c.-55C>A

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001388606 SCV001589664 pathogenic Haim-Munk syndrome; Periodontitis, aggressive 1; Papillon-Lefèvre syndrome 2020-04-12 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with Papillon Lefevre syndrome (PMID: 23108224). It has also been observed to segregate with disease in related individuals. This variant has been reported to affect CTSC protein function (PMID: 23108224). For these reasons, this variant has been classified as Pathogenic. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant occurs in a non-coding region of the CTSC gene. It does not change the encoded amino acid sequence of the CTSC protein.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323875 SCV004029338 pathogenic Papillon-Lefèvre syndrome 2023-07-17 criteria provided, single submitter clinical testing Variant summary: CTSC c.-55C>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 6.8e-06 in 147122 control chromosomes (gnomAD). c.-55C>A has been reported in the literature as a homozygous genotype in 4 unrelated Slovenian femalies affected with Papillon-Lefevre syndrome, segregating with disease (Kosem_2012). These data indicate that the variant is very likely to be associated with disease. The variant was found altering CTSC expression, where homozygous individuals had less than 2.5% expression when compared to controls, and less than 1.5% residual activity in peripheral leukocytes (Kosem_2012). The following publication has been ascertained in the context of this evaluation (PMID: 23108224). One ClinVar submitter has assessed the variant since 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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