Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Neuberg Centre For Genomic Medicine, |
RCV001823437 | SCV002072873 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy 1 | criteria provided, single submitter | clinical testing | The missense variant p.P392L in CHRNA4 (NM_000744.7) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.P392L variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between proline and leucine. In silico tools predict the variant to be tolearted and the residue is conserved across species. For these reasons, this variant has been classified as Uncertain Significance | |
| Neuberg Centre For Genomic Medicine, |
RCV002510596 | SCV002820291 | uncertain significance | Developmental and epileptic encephalopathy 94 | criteria provided, single submitter | clinical testing | The missense variant p.V230I in CHD2 (NM_001271.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to ClinVar as Uncertain significance. The missense variant c.688G>A (p.V230I) in CHD2 (NM_001271.4) is observed in 3/34404 (0.0087%) alleles from individuals of Latino background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. For these reasons, this variant has been classified as Uncertain Significance | |
| Labcorp Genetics |
RCV005057663 | SCV005704017 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2024-06-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 392 of the CHRNA4 protein (p.Pro392Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CHRNA4-related conditions (PMID: 36801247). ClinVar contains an entry for this variant (Variation ID: 1338983). 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 not expected to disrupt CHRNA4 protein function with a negative 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. |