ClinVar Miner

Submissions for variant NM_001242897.2(DEPDC5):c.2357C>T (p.Thr786Met) (rs564667614)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717165 SCV000848013 uncertain significance Seizures 2017-05-11 criteria provided, single submitter clinical testing The p.T864M variant (also known as c.2591C>T), located in coding exon 27 of the DEPDC5 gene, results from a C to T substitution at nucleotide position 2591. The threonine at codon 864 is replaced by methionine, an amino acid with similar properties. This variant was identified in an individual with temporal lobe epilepsy (Martin C et al. Clin. Genet., 2014 Dec;86:570-4). Functional studies on this alteration indicate no significant impact on protein function (van Kranenburg M et al. Hum. Mutat., 2015 Feb;36:200-9). This amino acid position is well conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence for this variant is conflicting at this time, the clinical significance remains unclear.
Invitae RCV001034645 SCV000964788 uncertain significance Familial focal epilepsy with variable foci 2020-10-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 864 of the DEPDC5 protein (p.Thr864Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs564667614, ExAC 0.05%). This variant has been observed in several individuals affected with epilepsy (PMID: 24283814, 28717674). ClinVar contains an entry for this variant (Variation ID: 180645). This variant has been reported not to substantially affect DEPDC5 protein function (PMID: 25366275). 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.
GeneDx RCV001564151 SCV001787264 likely benign not provided 2019-12-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30093711, 28717674, 24283814, 25366275)
OMIM RCV000157607 SCV000207416 pathogenic Epilepsy, familial focal, with variable foci 1 2014-12-01 no assertion criteria provided literature only
GeneReviews RCV000157607 SCV000321055 uncertain significance Epilepsy, familial focal, with variable foci 1 2016-04-13 no assertion criteria provided literature only

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