ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.325C>T (p.Arg109Cys)

gnomAD frequency: 0.00003  dbSNP: rs372337277
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001306123 SCV001495481 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-11-27 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 109 of the TBC1D24 protein (p.Arg109Cys). This variant is present in population databases (rs372337277, gnomAD 0.005%). 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: 800780). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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.
PreventionGenetics, part of Exact Sciences RCV004553525 SCV004107230 uncertain significance TBC1D24-related disorder 2023-09-15 criteria provided, single submitter clinical testing The TBC1D24 c.325C>T variant is predicted to result in the amino acid substitution p.Arg109Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2546474-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000984950 SCV001132864 uncertain significance Autosomal dominant nonsyndromic hearing loss 65 2019-01-29 no assertion criteria provided clinical testing

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