ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.641G>A (p.Arg214His) (rs200324356)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000118580 SCV000152986 uncertain significance not specified 2019-06-11 criteria provided, single submitter clinical testing
GeneDx RCV000118580 SCV000243335 likely benign not specified 2018-01-11 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,Partners HealthCare Personalized Medicine RCV000118580 SCV000272474 likely benign not specified 2019-03-01 criteria provided, single submitter clinical testing The p.Arg214His variant in TBC1D24 is classified as likely benign due to its high allele frequency. Although it has been reported in trans with a likely pathogenic variant in two Morroccan probands with hearing loss (2/272 alleles), it was also identified at a similar frequency in a race matched control population (1%, 4/400 chromosomes; Bakhchane 2015). Furthermore, this variant has been reported in several populations by gnomAD with a total allele frequency of 0.1% (271/280420) and an allele frequency of 0.19% (58/30602) of South Asian chromosomes including 1 homozygote. ACMG/AMP criteria: BS1.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000118580 SCV000297066 uncertain significance not specified 2015-09-24 criteria provided, single submitter clinical testing
Invitae RCV001084019 SCV000654212 likely benign Epileptic encephalopathy, early infantile, 1; Deafness, autosomal dominant 65; Caused by mutation in the TBC1 domain family, member 24 2020-12-03 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000661907 SCV000784228 uncertain significance Epileptic encephalopathy, early infantile, 1 2018-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000720472 SCV000851349 uncertain significance Seizures 2018-03-22 criteria provided, single submitter clinical testing The p.R214H variant (also known as c.641G>A), located in coding exon 1 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 641. The arginine at codon 214 is replaced by histidine, an amino acid with highly similar properties. This variant was identified with another TBC1D24 variant in three families with non-syndromic hearing loss; the variant was suggested to act as a hypomorph (Bakhchane A et al. PLoS ONE, 2015 Sep;10:e0138072; Rehman AU et al. Oral Dis, 2017 Jul;23:551-558). This variant was also detected in a patient with neonatal seizures and pervasive developmental disorder; however, the patient also had a de novo KCNQ2 mutation (Della Mina E et al. Eur. J. Hum. Genet., 2015 Mar;23:354-62). This amino acid position is highly 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.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000770979 SCV000897964 uncertain significance Deafness, autosomal recessive 86 2018-05-31 criteria provided, single submitter clinical testing This recessive variant was identified in two brothers diagnosed with profound bilateral hearing loss. Both patients harbour also a second variant (see below) in this gene in compound heterozygosity
Mendelics RCV000535912 SCV001135082 benign not provided 2019-05-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000535912 SCV001146070 likely benign not provided 2018-11-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000535912 SCV001150742 likely pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001120426 SCV001278910 benign Myoclonic epilepsy, familial infantile 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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