ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.676G>A (p.Ala226Thr)

gnomAD frequency: 0.00001  dbSNP: rs796053401
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189689 SCV000243336 uncertain significance not provided 2021-10-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Mayo Clinic Laboratories, Mayo Clinic RCV000189689 SCV001714539 uncertain significance not provided 2019-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852515 SCV002175113 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 226 of the TBC1D24 protein (p.Ala226Thr). This variant is present in population databases (rs796053401, gnomAD 0.003%). 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: 207502). 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.
Ambry Genetics RCV002514071 SCV003621471 uncertain significance Inborn genetic diseases 2022-05-18 criteria provided, single submitter clinical testing The c.676G>A (p.A226T) alteration is located in exon 2 (coding exon 1) of the TBC1D24 gene. This alteration results from a G to A substitution at nucleotide position 676, causing the alanine (A) at amino acid position 226 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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