Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189688 | SCV000243334 | uncertain significance | not provided | 2014-06-02 | criteria provided, single submitter | clinical testing | p.Ser202Leu (TCG>TTG): c.605 C>T in exon 2 of the TBC1D24 gene (NM_020705.2). A variant of unknown significance has been identified in the TBC1D24 gene. The S202L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S202L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, but not in more distantly related species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
| Labcorp Genetics |
RCV001303714 | SCV001492967 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2024-03-02 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 202 of the TBC1D24 protein (p.Ser202Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive TBC1D24-related conditions (PMID: 31922275). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 207501). 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. |
| Fulgent Genetics, |
RCV002478664 | SCV002788666 | 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 | 2021-07-27 | criteria provided, single submitter | clinical testing | |
| NIHR Bioresource Rare Diseases, |
RCV001003986 | SCV001162012 | likely pathogenic | Global developmental delay; Seizure; Specific learning disability; Cerebellar atrophy; Movement disorder | no assertion criteria provided | research |