Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001340848 | SCV001534681 | uncertain significance | Glycogen storage disease due to muscle and heart glycogen synthase deficiency | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 222 of the GYS1 protein (p.Asn222Lys). This variant is present in population databases (rs201548356, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GYS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1037659). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GYS1 protein function. 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. |