Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV002266682 | SCV002548746 | uncertain significance | Schaaf-Yang syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | The c.3384G>C (p.Arg1128Ser) variant identified in the MAGEL2 gene substitutes a well conserved Arginine for Serine at amino acid 1128/1250 (exon1/1). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.029) and Benign (PrimateAI; score:0.3485) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Arg1128 residue is not within a mapped domain of MAGEL2 (UniProtKB:Q9UJ55). Given the lack of compelling evidence for its pathogenicity, the c.3384G>C (p.Arg1128Ser) variant identified in the MAGEL2 gene is reported as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV003101516 | SCV003331763 | uncertain significance | not provided | 2022-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1128 of the MAGEL2 protein (p.Arg1128Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MAGEL2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |