Submissions for variant NM_001199107.2(TBC1D24):c.1570C>T (p.Arg524Trp)

gnomAD frequency: 0.00035  dbSNP: rs78644690

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218064	SCV000270885	likely benign	not specified	2015-11-12	criteria provided, single submitter	clinical testing	p.Arg524Trp in exon 8 of TBC1D24: This variant is not expected to have clinical significance because it has been identified in 0.33% (21/8102) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs78644690).
Ambry Genetics	RCV002315673	SCV000848950	uncertain significance	Inborn genetic diseases	2017-02-07	criteria provided, single submitter	clinical testing	The p.R524W variant (also known as c.1570C>T), located in coding exon 7 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 1570. The arginine at codon 524 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly 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 is limited at this time, the clinical significance of this variant remains unclear.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV001002765	SCV000992408	likely benign	Autosomal dominant nonsyndromic hearing loss 65		criteria provided, single submitter	case-control
Invitae	RCV000867209	SCV001008408	likely benign	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2024-01-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001120531	SCV001279023	uncertain significance	Familial infantile myoclonic epilepsy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001589120	SCV001824290	likely benign	not provided	2021-05-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24291220)
Department of Neurology, Xijing Hospital, Fourth Military Medical University	RCV002295290	SCV002553241	uncertain significance	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndrome	2022-03-01	criteria provided, single submitter	clinical testing