Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826208 | SCV000967773 | likely pathogenic | Glycogen storage disease | 2018-10-05 | criteria provided, single submitter | clinical testing | The p.Thr361GlnfsX2 variant in GYS2 has not been previously reported in individu als with glycogen storage disease type 0 but has been identified in 3/111606 of European chromosomes by the Genome Aggregation Database (gnomAD; http://gnomad.b roadinstitute.org). This variant is predicted to cause a frameshift, which alter s the protein?s amino acid sequence beginning at position 361 and leads to a pre mature termination codon 2 amino acids downstream. This alteration is then predi cted to lead to a truncated or absent protein. Loss of function of the GYS2 gene is a disease mechanism in autosomal recessive glycogen storage disease type 0. In summary, although additional studies are required to fully establish its cli nical significance, the p.Thr361GlnfsX2 variant is likely pathogenic. ACMG/AMP C riteria applied: PVS1_Strong, PM2. |
| Gene |
RCV001009065 | SCV001168875 | pathogenic | not provided | 2018-10-11 | criteria provided, single submitter | clinical testing | The c.1081delA variant in the GYS2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1081delA variant causes a frameshift starting with codon Threonine 361, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Thr361GlnfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1081delA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1081delA as a pathogenic variant. |