ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.217G>A (p.Val73Met)

gnomAD frequency: 0.00021  dbSNP: rs370078844
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000811679 SCV000951958 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2024-02-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 73 of the TBC1D24 protein (p.Val73Met). This variant is present in population databases (rs370078844, gnomAD 0.05%). 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: 655487). 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.
GeneDx RCV001576610 SCV001803835 uncertain significance not provided 2022-12-16 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24291220)
Ambry Genetics RCV002424907 SCV002730107 uncertain significance Inborn genetic diseases 2018-09-26 criteria provided, single submitter clinical testing The p.V73M variant (also known as c.217G>A), located in coding exon 1 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 217. The valine at codon 73 is replaced by methionine, an amino acid with highly similar properties. This variant was reported in an exome variant server sequencing project (Campeau PM et al. Lancet Neurol, 2014 Jan;13:44-58). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002495125 SCV002785066 uncertain significance Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndrome; DOORS syndrome; Familial infantile myoclonic epilepsy; Autosomal recessive nonsyndromic hearing loss 86; Developmental and epileptic encephalopathy, 16; Autosomal dominant nonsyndromic hearing loss 65 2022-01-04 criteria provided, single submitter clinical testing

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