Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000186925 | SCV000240496 | likely pathogenic | not provided | 2012-08-29 | criteria provided, single submitter | clinical testing | p.Trp182Arg (TGG>CGG):c.544 T>C in exon 5 of the CHRNA4 gene (NM_000744.5)The Trp182Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Trp182Arg in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged, non-polar Tryptophan residue is replaced by a positively charged Arginine residue. Trp182Arg alters a highly conserved position in the protein, and multiple in silico algorithms predict it is likely disease-causing. However, the Trp182Arg substitution does not occur within the transmembrane region of the protein, where pathogenic missense mutations have been identified (Steinlein et al., 2010). Therefore, based on the currently available information, Trp182Arg is a strong candidate for a disease-causing mutation, but the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s). |