Submissions for variant NM_001199107.2(TBC1D24):c.1642G>A (p.Val548Met)

gnomAD frequency: 0.00009  dbSNP: rs201649140

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727315	SCV000514861	likely benign	not provided	2021-05-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24291220)
Invitae	RCV001083452	SCV000560548	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
Athena Diagnostics Inc	RCV000727315	SCV000615751	uncertain significance	not provided	2018-10-04	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727315	SCV000707486	uncertain significance	not provided	2018-01-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000444565	SCV000711640	likely benign	not specified	2017-02-07	criteria provided, single submitter	clinical testing	p.Val548Met in exon 8 of TBC1D24: This variant is not expected to have clinical significance because it has been identified in 0.4% (48/11428 and 142/36466) of Latino chromosomes including one homozygote by the Exome Aggregation Consortium and the Genome Aggregation Database respectively (ExAC, http://exac.broadinstitu te.org; gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201649140).
Ambry Genetics	RCV002314161	SCV000848447	uncertain significance	Inborn genetic diseases	2019-06-24	criteria provided, single submitter	clinical testing	The p.V548M variant (also known as c.1642G>A), located in coding exon 7 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 1642. The valine at codon 548 is replaced by methionine, an amino acid with highly similar 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. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Illumina Laboratory Services, Illumina	RCV001120532	SCV001279024	likely benign	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 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.
PreventionGenetics, part of Exact Sciences	RCV003922717	SCV004740453	likely benign	TBC1D24-related condition	2023-09-13	criteria provided, single submitter	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).