Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001036363 | SCV001199724 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2021-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 327 of the CHRNA4 protein (p.Val327Met). This variant is present in population databases (rs201841018, gnomAD 0.006%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 835474). This missense change has been observed in at least one individual who was not affected with CHRNA4-related conditions (Invitae). This missense change has been observed in individual(s) with dyskinesia, dystonia, and/or seizures (PMID: 29454195). |
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, |
RCV001095404 | SCV001251112 | likely benign | Amyotrophic lateral sclerosis | 2020-03-31 | criteria provided, single submitter | research |