Submissions for variant NM_001242896.3(DEPDC5):c.113T>C (p.Ile38Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003110368	SCV003780190	uncertain significance	Familial focal epilepsy with variable foci	2024-05-13	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 38 of the DEPDC5 protein (p.Ile38Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 2413365). 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 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.
Neuberg Centre For Genomic Medicine, NCGM	RCV003340660	SCV004046942	uncertain significance	Epilepsy, familial focal, with variable foci 1		criteria provided, single submitter	clinical testing	The missense c.113T>C (p.Ile38Thr) variant in DEPDC5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ile38Thr variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Ile at position 38 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The amino acid change p.Ile38Thr in DEPDC5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.