Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000690024 | SCV000817700 | uncertain significance | Febrile seizures, familial, 11 | 2022-12-02 | criteria provided, single submitter | clinical testing | 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. 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 CPA6 protein function. ClinVar contains an entry for this variant (Variation ID: 569405). This variant has not been reported in the literature in individuals affected with CPA6-related conditions. This variant is present in population databases (rs183899632, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 36 of the CPA6 protein (p.Arg36Leu). |
| New York Genome Center | RCV001281571 | SCV001468881 | uncertain significance | Seizure | 2019-08-14 | criteria provided, single submitter | clinical testing | The c.107G>T (p.Arg36Leu) variant identified it the CPA6 gene substitutes a moderately conserved Arginine for Leucine at amino acid 36. This variant is found in gnomAD (15 heterozygotes, 0 homozygotes; allele frequency: 5.32e-5) and ExAC (5 heterozygotes, 0 homozygotes; allele frequency: 4.18e-5). In silico algorithms predict this variant to be Neutral (Provean; score: -2.36) and Damaging (SIFT; score: 0.013) to the function of the canonical transcript. This variant is classified in ClinVar as a Varaint of Uncertain Significance (VarID: 569405), and while the c.107G>T (p.Arg36Leu) variant identified in this individual has never been reported in the literature, a different change at the same nucleotide has been reported. A c.107G>A (p.Arg36His) variant in the CPA6 gene was reported in a female with Juvenile Myoclonic Epilepsy [PMID: 25875328]. The reported patient was described with myoclonic seizures, generalized tonic-clonic seizures, and absence seizures that were onset at 16.5 years of age. Functional studies on the p.Arg36His variant demonstrated 50% reduction of the mutant protein in the extracellular matrix [PMID: 25875328]. While a variant at the same nucleotide has been reported in an individual affected with epilepsy, the lack of functional data or additional evidence supporting the pathogenicity for the c.107G>T (p.Arg36Leu) variant identified in this patient results in its report here as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV001334071 | SCV001526811 | uncertain significance | Familial temporal lobe epilepsy 5 | 2018-01-30 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Fulgent Genetics, |
RCV002477549 | SCV002782049 | uncertain significance | Familial temporal lobe epilepsy 5; Febrile seizures, familial, 11 | 2021-08-04 | criteria provided, single submitter | clinical testing |