Submissions for variant NM_003793.4(CTSF):c.993_1004delinsTGCCTACT (p.Lys331fs)

dbSNP: rs2134951897

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mayo Clinic Laboratories, Mayo Clinic	RCV002254506	SCV002525804	pathogenic	not provided	2021-05-18	criteria provided, single submitter	clinical testing	PVS1, PM2, PP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002509766	SCV002819741	likely pathogenic	Neuronal ceroid lipofuscinosis	2022-12-22	criteria provided, single submitter	clinical testing	Variant summary: CTSF c.993_1004delinsTGCCTACT (p.Lys331AsnfsX14) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and are associated with Kufs disease, type B in HGMD. The variant was absent in 251352 control chromosomes. c.993_1004delinsTGCCTACT has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Kulkarni_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.