Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000255677 | SCV000321405 | likely pathogenic | not provided | 2017-02-02 | criteria provided, single submitter | clinical testing | A R330H variant that is likely pathogenic has been identified in the ARX gene. The R330H 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R332C, R332H, R332P, T333S, T333N) have been reported in the Human Gene Mutation Database in association with ARX-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, the R330H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Institute of Human Genetics, |
RCV001253064 | SCV001428586 | likely pathogenic | Developmental and epileptic encephalopathy, 1 | 2017-09-12 | criteria provided, single submitter | clinical testing | This variant was identified as hemizygous |