ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.1456C>T (p.Arg486Cys)

gnomAD frequency: 0.00009  dbSNP: rs750028854
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001036955 SCV001200345 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-11-28 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 486 of the TBC1D24 protein (p.Arg486Cys). This variant is present in population databases (rs750028854, gnomAD 0.01%). 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: 835949). 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 expected to disrupt TBC1D24 protein function with a positive 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.
GeneDx RCV001564062 SCV001787164 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002552469 SCV003617687 uncertain significance Inborn genetic diseases 2022-04-28 criteria provided, single submitter clinical testing The c.1456C>T (p.R486C) alteration is located in exon 7 (coding exon 6) of the TBC1D24 gene. This alteration results from a C to T substitution at nucleotide position 1456, causing the arginine (R) at amino acid position 486 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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