Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704421 | SCV000833370 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 624 of the KCNQ2 protein (p.Gly624Arg). This variant is present in population databases (rs771211103, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580776). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Prevention |
RCV003424299 | SCV004118403 | uncertain significance | KCNQ2-related condition | 2023-09-11 | criteria provided, single submitter | clinical testing | The KCNQ2 c.1870G>A variant is predicted to result in the amino acid substitution p.Gly624Arg. This variant was reported in an individual with alternating hemiplegia of childhood; however, this individual carried additional candidate variants of uncertain significance, and the KCNQ2 variant was inherited from an unaffected father and absent from an affected sibling (Pavone et al. 2022. PubMed ID: 35177115). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-62039783-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |