Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000692790 | SCV000820633 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1675 of the CACNA1H protein (p.Arg1675Gln). This variant is present in population databases (rs149367557, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with seizures (PMID: 27066544). This variant is also known as p.Arg1669Gln. ClinVar contains an entry for this variant (Variation ID: 571604). 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. |
Gene |
RCV004719951 | SCV005325400 | uncertain significance | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | Identified in a patient with epilepsy with auditory features who inherited the variant from a parent with sleep-related bilateral tonic-clonic seizures (Pippucci et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27066544) |