ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.268dup (p.Gln90fs)

dbSNP: rs752612332
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494186 SCV000582866 pathogenic not provided 2017-05-22 criteria provided, single submitter clinical testing The c.268dupC pathogenic variant in the CTSD gene has been reported previously as a homozygous change in two siblings with myoclonic epilepsy, respiratory failure, and cathepsin D deficiency (Meyer et al., 2015). Due to use of alternative nomenclature, this variant has been reported as c.268_269insC (Meyer et al., 2015). The c.268dupC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The duplication causes a frameshift starting with codon Glutamine 90, changes this amino acid to a Proline residue and creates a premature Stop codon at position 50 of the new reading frame, denoted p.Gln90ProfsX50. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Labcorp Genetics (formerly Invitae), Labcorp RCV002527103 SCV003292943 pathogenic Neuronal ceroid lipofuscinosis 2024-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln90Profs*50) in the CTSD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTSD are known to be pathogenic (PMID: 16670177, 26059544). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (PMID: 26059544, 29373990). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 430138). For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796203 SCV005416791 pathogenic Neuronal ceroid lipofuscinosis 10 criteria provided, single submitter clinical testing PM2_Supporting+PVS1+PM3_Supporting+PP1_Moderate

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.