ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.299C>T (p.Ser100Phe) (rs796052407)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187320 SCV000240902 likely pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing The S100F variant in the CTSD gene has been reported previously in an individual with congenital neuronal lipofuscinosis who was homozygous for the S100F variant (Fritchie et al., 2009). Functional studies of the S100F variant demonstrated a damaging effect with severely reduced cathepsin D enzyme activity (Fritchie et al., 2009). The S100F variant is not observed in large population cohorts (Lek et al., 2016). The S100F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret S100F as a likely pathogenic variant.
Invitae RCV001207662 SCV001379025 uncertain significance Neuronal ceroid lipofuscinosis 2020-02-23 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 100 of the CTSD protein (p.Ser100Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in the homozygous state in an individual affected with congenital neuronal ceroid lipofuscinosis (PMID: 18762956). ClinVar contains an entry for this variant (Variation ID: 205363). This variant has been reported to affect CTSD protein function (PMID: 18762956). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.