Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002909359 | SCV003255998 | uncertain significance | Glycogen storage disease, type II | 2022-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 609 of the GAA protein (p.Tyr609His). This variant is present in population databases (rs778892297, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. 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) performed at Invitae indicates that this missense variant is expected to disrupt GAA 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. |
| Ambry Genetics | RCV004990916 | SCV005591980 | uncertain significance | Cardiovascular phenotype | 2024-11-10 | criteria provided, single submitter | clinical testing | The p.Y609H variant (also known as c.1825T>C), located in coding exon 12 of the GAA gene, results from a T to C substitution at nucleotide position 1825. The tyrosine at codon 609 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |