Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188932 | SCV000242563 | likely pathogenic | not provided | 2017-07-13 | criteria provided, single submitter | clinical testing | p.Trp1284Arg (TGG>CGG): c.3850 T>C in exon 19 of the SCN1A gene (NM_001165963.1) The Trp1284Arg missense change has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of an uncharged, non-polar Tryptophan residue with a positively charged Arginine residue. The variant alters a highly conserved position in the S3 subunit in the third transmembrane domain of the protein. A different amino acid substitution at this position (Trp1284Ser) has been published in association with Dravet syndrome. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, Trp1284Arg is a strong candidate for a pathogenic variant, although the possibility that it is a benign variant cannot be excluded. |
Centre for Inherited Metabolic Diseases, |
RCV001375621 | SCV001572543 | likely pathogenic | Severe myoclonic epilepsy in infancy | 2021-04-25 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV002247609 | SCV002519018 | pathogenic | Generalized epilepsy with febrile seizures plus, type 2 | 2022-05-04 | criteria provided, single submitter | clinical testing |