Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000144323 | SCV002540710 | uncertain significance | Angelman syndrome | 2022-06-30 | reviewed by expert panel | curation | The c.349T>C p.(Cys117Arg) variant in UBE3A (NM_130838.2) is absent from gnomAD (PM2_supporting). The p.(Cys117Arg) variant has been observed in at least 3 individuals with a clinical phenotype suggestive of Angelman syndrome (PMID 25212744, ClinVar SCV000570280.3) (PS4_moderate, PP4). Computational prediction analysis tools are inconclusive for this variant. In summary, the c.349T>C p.(Cys117Arg) variant in UBE3A is classified as a Variant of Unknown Significance based on the ACMG/AMP criteria (PS4_moderate, PP4, PM2_supporting). |
Gene |
RCV000483509 | SCV000570280 | likely pathogenic | not provided | 2016-05-17 | criteria provided, single submitter | clinical testing | The C117R variant has been reported previously in two individuals with suspected Angelman syndrome and in one of these cases was found to be maternally inherited (Sadikovic et al., 2014). Functional studies suggest that C117R results in protein instability (Yi et al., 2015). 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. The C117R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. 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. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Baylor Genetics | RCV000144323 | SCV000188500 | uncertain significance | Angelman syndrome | 2014-02-14 | no assertion criteria provided | clinical testing | possible diagnosis of Angelman syndrome |