Submissions for variant NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)

gnomAD frequency: 0.00016  dbSNP: rs79027628

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193474	SCV000247184	uncertain significance	not specified	2015-02-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001034651	SCV000546537	uncertain significance	Familial focal epilepsy with variable foci	2024-01-28	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1104 of the DEPDC5 protein (p.Ser1104Leu). This variant is present in population databases (rs79027628, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of DEPDC5-related conditions (PMID: 23542697, 29356177, 31139143, 31594065). ClinVar contains an entry for this variant (Variation ID: 210846). 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.
Ambry Genetics	RCV002317677	SCV000851156	likely benign	Inborn genetic diseases	2019-06-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV000254574	SCV000895416	uncertain significance	Epilepsy, familial focal, with variable foci 1	2018-10-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000254574	SCV001141410	uncertain significance	Epilepsy, familial focal, with variable foci 1	2019-05-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000254574	SCV001525504	uncertain significance	Epilepsy, familial focal, with variable foci 1	2019-04-19	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This c.3311C>T (p.S1104L) variant has been previously reported in patients with FFEVF1 or paroxysmal kinesigenic dyskinesia [PMID 23542697, 29356177], however, another study found this variant lacks strong segregation support [PMID 28717674]
GeneDx	RCV001668361	SCV001889294	benign	not provided	2020-06-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31639411, 31594065, 31139143, 30093711, 28717674, 23542697, 29356177, 25366275, 27683934)
Revvity Omics, Revvity	RCV001668361	SCV003834327	uncertain significance	not provided	2022-04-07	criteria provided, single submitter	clinical testing
GeneReviews	RCV000254574	SCV000321059	not provided	Epilepsy, familial focal, with variable foci 1		no assertion provided	literature only
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV000254574	SCV001432416	likely benign	Epilepsy, familial focal, with variable foci 1		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751356	SCV005359242	likely benign	DEPDC5-related disorder	2024-07-22	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).