ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.343C>T (p.Arg115Cys)

gnomAD frequency: 0.00008  dbSNP: rs372531999
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189682 SCV000243328 uncertain significance not provided 2023-06-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002314767 SCV000849436 uncertain significance Inborn genetic diseases 2018-11-16 criteria provided, single submitter clinical testing The p.R115C variant (also known as c.343C>T), located in coding exon 1 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 343. The arginine at codon 115 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001058657 SCV001223244 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2025-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 115 of the TBC1D24 protein (p.Arg115Cys). This variant is present in population databases (rs372531999, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. ClinVar contains an entry for this variant (Variation ID: 207496). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TBC1D24 protein function with a negative predictive value of 80%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000189682 SCV004227510 uncertain significance not provided 2023-05-05 criteria provided, single submitter clinical testing BP4, PM2

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