Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Lupski Lab, |
RCV000192066 | SCV000266465 | pathogenic | DOORS syndrome | 2014-01-01 | criteria provided, single submitter | research | We identified 26 families with DOORS syndrome; each patient had at least 3 of the 5 well-described features of DOORS syndrome, which include deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. A combination of whole-exome sequencing and Sanger sequencing identified homozygous or compound heterozygous pathogenic variants in TBC1D24 in 11 individuals from 9 families. |
| Labcorp Genetics |
RCV001850282 | SCV002311889 | likely pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2023-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 40 of the TBC1D24 protein (p.Arg40Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive DOORS syndrome (PMID: 24291220). ClinVar contains an entry for this variant (Variation ID: 183152). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TBC1D24 function (PMID: 27281533, 30335140). This variant disrupts the p.Arg40 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been observed in individuals with TBC1D24-related conditions (PMID: 24291220; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Division of Medical Genetics; Sainte- |
RCV000192066 | SCV000211964 | pathogenic | DOORS syndrome | 2014-12-22 | no assertion criteria provided | literature only | |
| Gene |
RCV000192066 | SCV002106357 | not provided | DOORS syndrome | no assertion provided | literature only |