Submissions for variant NM_001199107.2(TBC1D24):c.169C>T (p.Arg57Cys)

gnomAD frequency: 0.00121  dbSNP: rs202162520

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189679	SCV000243325	benign	not specified	2019-07-22	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000189679	SCV000269860	benign	not specified	2015-07-16	criteria provided, single submitter	clinical testing	p.Arg57Cys in exon 2 of TBC1D24: This variant is not expected to have clinical s ignificance it has been identified in 0.3% (182/65958) of European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs202162520).
Eurofins Ntd Llc (ga)	RCV000585579	SCV000332349	uncertain significance	not provided	2017-02-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000340164	SCV000396203	likely benign	Familial infantile myoclonic epilepsy	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV001084629	SCV000560545	benign	Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24	2024-01-29	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000189679	SCV000615752	uncertain significance	not specified	2016-10-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585579	SCV000692828	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	TBC1D24: BP4
Ambry Genetics	RCV002314614	SCV000847922	uncertain significance	Inborn genetic diseases	2019-05-01	criteria provided, single submitter	clinical testing	The p.R57C variant (also known as c.169C>T), located in coding exon 1 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 169. The arginine at codon 57 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on data from gnomAD, the T allele has an overall frequency of approximately 0.18% (507/27762) total alleles studied. The highest observed frequency was 1.06% (107/10138) of Ashkenazi Jewish alleles. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000585579	SCV004562323	likely benign	not provided	2023-09-11	criteria provided, single submitter	clinical testing
Bioinformatics Core, Luxembourg Center for Systems Biomedicine	RCV000656037	SCV000588313	pathogenic	Childhood epilepsy with centrotemporal spikes	2017-01-01	no assertion criteria provided	case-control	CAADphred>15
GenomeConnect, ClinGen	RCV000585579	SCV000840178	not provided	not provided		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.