Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV000626019 | SCV000746628 | pathogenic | Developmental and epileptic encephalopathy, 44 | 2021-03-14 | criteria provided, single submitter | clinical testing | Functional analyses demonstrated that the p.Cys303Arg variant results in a significant decrease in protein function. See PMID: 33811063. ACMG criteria applied: PS3, PM2, PM3, PP3, PP4. |
Broad Center for Mendelian Genomics, |
RCV000626019 | SCV000786705 | uncertain significance | Developmental and epileptic encephalopathy, 44 | criteria provided, single submitter | research | The heterozygous p.Cys303Arg variant was identified in the compound heterozygous state by our study in one individual with Epileptic Encephalopathy. The p.Cys303Arg variant has not been reported in the literature and was absent from large population studies. The cysteine (cys) at position 303 is highly conserved in mammals and evolutionary distant species, raising the possibility/supporting that a change at this position may not be tolerated. Computational tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Cys303Arg variant is uncertain. |