Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000313359 | SCV000337526 | uncertain significance | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000671751 | SCV000796767 | uncertain significance | Glycogen storage disease, type II | 2017-12-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000671751 | SCV001233298 | likely pathogenic | Glycogen storage disease, type II | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 746 of the GAA protein (p.Trp746Leu). This variant is present in population databases (rs752921215, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for GAA-related disease (PMID: 23430949). ClinVar contains an entry for this variant (Variation ID: 284776). 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 with a positive predictive value of 95%. This variant disrupts the p.Trp746 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7981676, 9535769, 21232767, 21757382, 25093132, 27099502). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Genome- |
RCV000671751 | SCV002027299 | uncertain significance | Glycogen storage disease, type II | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000313359 | SCV003816215 | uncertain significance | not provided | 2023-02-28 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000671751 | SCV002092117 | uncertain significance | Glycogen storage disease, type II | 2020-10-07 | no assertion criteria provided | clinical testing |