ClinVar Miner

Submissions for variant NM_001242897.2(DEPDC5):c.1663C>T (p.Arg555Ter) (rs587776973)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001034675 SCV000642163 pathogenic Familial focal epilepsy with variable foci 2019-08-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg555*) in the DEPDC5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in families affected with focal epilepsy (PMID: 23542697, 26000329, 28102150). ClinVar contains an entry for this variant (Variation ID: 50820). Loss-of-function variants in DEPDC5 are known to be pathogenic (PMID: 23542697, 23542701). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000720916 SCV000851800 pathogenic Seizures 2017-09-20 criteria provided, single submitter clinical testing The p.R555* pathogenic mutation (also known as c.1663C>T), located in coding exon 20 of the DEPDC5 gene, results from a C to T substitution at nucleotide position 1663. This changes the amino acid from an arginine to a stop codon within coding exon 20. In one study, this mutation was detected in 25 individuals from a single Dutch family showing incomplete (56%) penetrance. 14 of the 25 individuals who carried the mutation in this family suffered from one or more of the following seizure types: frontal, frontotemporal, temporal, nocturnal frontal, and/or multi focal (Dibbens LM, et al. Nat. Genet. 2013;45(5):546-51). In another study, this mutation was detected in two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia. The mutation was paternally inherited, and the father had four nocturnal tonic clonic seizures and one daytime seizure beginning at age 24 (Scerri T, et al. Ann Clin Transl Neurol 2015 May; 2(5):575-80). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091571 SCV001247697 pathogenic not provided 2018-04-01 criteria provided, single submitter clinical testing
OMIM RCV000043580 SCV000071579 pathogenic Epilepsy, familial focal, with variable foci 1 2013-05-01 no assertion criteria provided literature only
GeneReviews RCV000043580 SCV000321026 pathogenic Epilepsy, familial focal, with variable foci 1 2016-04-13 no assertion criteria provided literature only

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