ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.956C>T (p.Pro319Leu)

gnomAD frequency: 0.00001  dbSNP: rs373170074
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187318 SCV000240900 uncertain significance not provided 2014-12-02 criteria provided, single submitter clinical testing p.Pro319Leu (CCG>CTG): c.956 C>T in exon 7 of the CTSD gene (NM_001909.4). A variant of unknown significance has been identified in the CTSD gene. The P319L variant has not been published as a mutation, nor has it been reported as a benign polymorphism . It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P319L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a highly conserved position predicted to be within the Cathepsin D heavy chain of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
Invitae RCV001044040 SCV001207814 uncertain significance Neuronal ceroid lipofuscinosis 2022-05-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 319 of the CTSD protein (p.Pro319Leu). This variant is present in population databases (rs373170074, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CTSD-related conditions. ClinVar contains an entry for this variant (Variation ID: 205361). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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