Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000536887 | SCV000626580 | uncertain significance | Glycogen storage disease, type II | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 841 of the GAA protein (p.Met841Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GAA-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 456409). 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 not expected to disrupt GAA protein function with a negative predictive value of 95%. 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 | RCV002456048 | SCV002738718 | uncertain significance | Cardiovascular phenotype | 2021-09-07 | criteria provided, single submitter | clinical testing | The p.M841V variant (also known as c.2521A>G), located in coding exon 17 of the GAA gene, results from an A to G substitution at nucleotide position 2521. The methionine at codon 841 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV000536887 | SCV002790391 | uncertain significance | Glycogen storage disease, type II | 2021-09-04 | criteria provided, single submitter | clinical testing |