ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.505C>G (p.Leu169Val) (rs768487717)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717869 SCV000848729 uncertain significance Seizures 2017-01-16 criteria provided, single submitter clinical testing The p.L169V variant (also known as c.505C>G), located in coding exon 5 of the CTSD gene, results from a C to G substitution at nucleotide position 505. The leucine at codon 169 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV001348162 SCV001542452 uncertain significance Neuronal ceroid lipofuscinosis 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 169 of the CTSD protein (p.Leu169Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs768487717, ExAC 0.009%). This variant has not been reported in the literature in individuals with CTSD-related conditions. ClinVar contains an entry for this variant (Variation ID: 588664). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV001555248 SCV001776629 uncertain significance not provided 2020-12-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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