ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.956C>T (p.Pro319Leu) (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 2020-03-06 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 319 of the CTSD protein (p.Pro319Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals 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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