Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001215128 | SCV001386855 | likely pathogenic | Familial focal epilepsy with variable foci | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 191 of the DEPDC5 protein (p.Tyr191Cys). This variant is present in population databases (rs749809456, gnomAD 0.01%). This missense change has been observed in individuals with autosomal dominant DEPDC5-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 944676). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
New York Genome Center | RCV001542435 | SCV001761138 | uncertain significance | Epilepsy, familial focal, with variable foci 1 | 2020-07-03 | criteria provided, single submitter | clinical testing | The inherited heterozygous p.Tyr191Cys variant identified in the DEPDC5 gene has not been reported in affected individuals in the literature to the best of our knowledge. The variant has 0.00002095 allele frequency in the gnomAD(v3) database (3 out of 143,182 heterozygotes, no homozygote) indicating it is a rare allele in thegeneral population. The affected residue is evolutionarily conserved.The variant is predicted deleterious by multiple in silico prediction tools. Functional studies to evaluate the potential pathogenicity of this variant have not been reported in the literature. Based on the current evidence, the inherited p.Tyr191Cys variant in the DEPDC5 gene is assessed as a variant of uncertain significance. |
Unidad de Genómica Garrahan, |
RCV002283530 | SCV002573452 | likely pathogenic | Continuous spike and waves during slow sleep | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002348716 | SCV002650652 | uncertain significance | Inborn genetic diseases | 2018-01-29 | criteria provided, single submitter | clinical testing | The p.Y191C variant (also known as c.572A>G), located in coding exon 9 of the DEPDC5 gene, results from an A to G substitution at nucleotide position 572. The tyrosine at codon 191 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |