Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193579 | SCV001362498 | pathogenic | Glycogen storage disease, type II | 2019-07-25 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.1913G>T (p.Gly638Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241884 control chromosomes. c.1913G>T has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (van den Hout_2004, Oba-Shinjo_2009). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (van den Hout_2009). The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001193579 | SCV001585656 | pathogenic | Glycogen storage disease, type II | 2021-06-01 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Gly638 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10737124, 29181627, 18429042, 29122469, 19588081, 17573812, 28763149). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in individual(s) with Pompe disease (PMID: 15121988, 19588081). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 928930). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 638 of the GAA protein (p.Gly638Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV001780099 | SCV002023805 | pathogenic | not provided | 2022-02-20 | criteria provided, single submitter | clinical testing |