Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000483105 | SCV000571531 | uncertain significance | not provided | 2016-08-29 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CHRNA2 gene. The I145V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I145V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Ambry Genetics | RCV002318578 | SCV000851223 | uncertain significance | Inborn genetic diseases | 2016-09-07 | criteria provided, single submitter | clinical testing | The p.I145V variant (also known as c.433A>G), located in coding exon 4 of the CHRNA2 gene, results from an A to G substitution at nucleotide position 433. The isoleucine at codon 145 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001851224 | SCV002302584 | likely benign | Autosomal dominant nocturnal frontal lobe epilepsy | 2022-08-16 | criteria provided, single submitter | clinical testing |