Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000116719 | SCV000150690 | uncertain significance | not provided | 2013-10-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000116719 | SCV000240523 | uncertain significance | not provided | 2018-02-05 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CHRNA4 gene. The A509T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A509T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The A509T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, 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). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter 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 | RCV000624743 | SCV000742167 | uncertain significance | Inborn genetic diseases | 2017-06-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000624743 | SCV000848931 | uncertain significance | Inborn genetic diseases | 2017-02-28 | criteria provided, single submitter | clinical testing | The p.A509T variant (also known as c.1525G>A), located in coding exon 5 of the CHRNA4 gene, results from a G to A substitution at nucleotide position 1525. The alanine at codon 509 is replaced by threonine, an amino acid with similar properties. This amino acid position is not 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. |
Invitae | RCV002512515 | SCV003285204 | likely benign | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-11-12 | criteria provided, single submitter | clinical testing |