Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000720915 | SCV000851799 | uncertain significance | Seizures | 2016-02-02 | criteria provided, single submitter | clinical testing | The p.N315S variant (also known as c.944A>G), located in coding exon 13 of the DEPDC5 gene, results from an A to G substitution at nucleotide position 944. The asparagine at codon 315 is replaced by serine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6017 samples (12034 alleles) with coverage at this position. This amino acid position is highly 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 variantremains unclear. |
| Invitae | RCV000798876 | SCV000938515 | uncertain significance | Familial focal epilepsy with variable foci | 2019-03-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 944 of the DEPDC5 protein (p.Asn315Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs555944888, ExAC 0.04%). This variant has not been reported in the literature in individuals with DEPDC5-related disease. 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: "Not Available"; Align-GVGD: "Class C45"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |