Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000809511 | SCV000949664 | likely pathogenic | Glycogen storage disease, type VI | 2022-01-19 | criteria provided, single submitter | clinical testing | 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. 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 PYGL protein function. ClinVar contains an entry for this variant (Variation ID: 653702). This missense change has been observed in individual(s) with Glycogen storage disease and/or Glycogen storage disorder (PMID: 33763395; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs760187622, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 809 of the PYGL protein (p.Ser809Leu). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000809511 | SCV004020901 | pathogenic | Glycogen storage disease, type VI | 2023-06-30 | criteria provided, single submitter | clinical testing | Variant summary: PYGL c.2426C>T (p.Ser809Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251466 control chromosomes. c.2426C>T has been reported in the literature in multiple individuals affected with Glycogen storage disease, type VI (Fang_2021, Luo_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33763395, 35143115). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |