Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705309 | SCV000834299 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2018-01-28 | criteria provided, single submitter | clinical testing | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CHRNA4-related disease. ClinVar contains an entry for this variant (Variation ID: 98311). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces cysteine with tyrosine at codon 422 of the CHRNA4 protein (p.Cys422Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Ambry Genetics | RCV002444556 | SCV002679961 | uncertain significance | Inborn genetic diseases | 2017-06-15 | criteria provided, single submitter | clinical testing | The p.C422Y variant (also known as c.1265G>A), located in coding exon 5 of the CHRNA4 gene, results from a G to A substitution at nucleotide position 1265. The cysteine at codon 422 is replaced by tyrosine, an amino acid with highly dissimilar 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. |
| Psychiatry Genetics Yale University | RCV000084601 | SCV000116737 | not provided | Tobacco use disorder | no assertion provided | not provided |