ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.1453G>A (p.Ala485Thr)

gnomAD frequency: 0.00006  dbSNP: rs774586263
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000428266 SCV000528163 uncertain significance not provided 2022-12-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001069475 SCV001234642 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-11-18 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 485 of the TBC1D24 protein (p.Ala485Thr). This variant is present in population databases (rs774586263, 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: 386478). 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 95%. 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.
CeGaT Center for Human Genetics Tuebingen RCV000428266 SCV001501588 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing TBC1D24: PM2, BP4
Ambry Genetics RCV002393011 SCV002701893 uncertain significance Inborn genetic diseases 2020-04-27 criteria provided, single submitter clinical testing The p.A485T variant (also known as c.1453G>A), located in coding exon 6 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 1453. The alanine at codon 485 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other 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.

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