Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001967690 | SCV002219970 | uncertain significance | Glycogen storage disease, type II | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 669 of the GAA protein (p.Pro669Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with GAA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002423109 | SCV002721721 | uncertain significance | Cardiovascular phenotype | 2022-03-22 | criteria provided, single submitter | clinical testing | The p.P669T variant (also known as c.2005C>A), located in coding exon 13 of the GAA gene, results from a C to A substitution at nucleotide position 2005. The proline at codon 669 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |