Submissions for variant NM_001199107.2(TBC1D24):c.1079G>T (p.Arg360Leu)

dbSNP: rs765965968

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Snyder Lab, Genetics Department, Stanford University	RCV000678490	SCV000804198	pathogenic	Intellectual disability; Periodic paralysis; Neurodevelopmental delay	2018-08-27	criteria provided, single submitter	case-control
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814074	SCV001755529	likely pathogenic	Abnormality of the nervous system	2021-07-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001850283	SCV002178644	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2022-08-16	criteria provided, single submitter	clinical testing	The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Experimental studies have shown that this missense change affects TBC1D24 function (PMID: 27281533, 30335140). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 183157). This missense change has been observed in individual(s) with clinical features of autosomal recessive TBC1D24-related conditions (PMID: 25401298). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 360 of the TBC1D24 protein (p.Arg360Leu).
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002468571	SCV002764926	pathogenic	Developmental and epileptic encephalopathy, 16	2021-06-08	criteria provided, single submitter	clinical testing
Division of Medical Genetics; Sainte-Justine Hospital	RCV000192071	SCV000211974	pathogenic	Epilepsy, progressive myoclonic, 1B	2014-12-22	no assertion criteria provided	literature only