ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.1525G>A (p.Gly509Arg)

gnomAD frequency: 0.00002  dbSNP: rs749994791
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000488051 SCV000575032 uncertain significance not provided 2016-12-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000704799 SCV000833766 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2022-08-31 criteria provided, single submitter clinical testing This variant is present in population databases (rs749994791, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 509 of the TBC1D24 protein (p.Gly509Arg). This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 425091).
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV003335374 SCV004045865 likely pathogenic Developmental and epileptic encephalopathy, 16 2023-01-27 criteria provided, single submitter clinical testing

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