Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000818611 | SCV000959233 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 821 of the CACNA1H protein (p.Leu821Val). This variant is present in population databases (rs777617840, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 661236). 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 CACNA1H protein function with a positive 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. |
Athena Diagnostics | RCV000991765 | SCV001143474 | uncertain significance | not provided | 2019-01-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002535479 | SCV003534643 | uncertain significance | Inborn genetic diseases | 2021-09-14 | criteria provided, single submitter | clinical testing | The c.2461C>G (p.L821V) alteration is located in exon 11 (coding exon 10) of the CACNA1H gene. This alteration results from a C to G substitution at nucleotide position 2461, causing the leucine (L) at amino acid position 821 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV005021246 | SCV005643257 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV | 2024-01-26 | criteria provided, single submitter | clinical testing |