Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535769 | SCV000634063 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 751 of the KCNQ2 protein (p.Ser751Leu). This variant is present in population databases (rs774002673, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. 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: 339329). 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 tolerated. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 35104249). 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. |
New York Genome Center | RCV001542406 | SCV001761105 | uncertain significance | Developmental and epileptic encephalopathy, 7 | 2020-07-03 | criteria provided, single submitter | clinical testing | |
Channelopathy- |
RCV003315337 | SCV004015039 | not provided | Complex neurodevelopmental disorder | no assertion provided | literature only |