Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000020499 | SCV003934852 | likely pathogenic | Glycogen storage disease, type VI | 2023-05-24 | criteria provided, single submitter | clinical testing | Variant summary: PYGL c.2024C>T (p.Ser675Leu) results in a non-conservative amino acid change located in the pyridoxal-phosphate attachment site (amino acids 673-685; IPR035090) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251462 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2024C>T has been reported in the literature in multiple compound heterozygous individuals, including two siblings, affected with Glycogen storage disease, type VI (e.g., Beaucham_2007, Davit-Spraul_2011, Luo_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, several studies note that the variant is expected to disrupt hydrogen bonding in the active site and therefore is predicted to disrupt enzyme activity (e.g., Beauchamp_2007, Liu_2020). The following publications have been ascertained in the context of this evaluation (PMID: 17705025, 21646031, 35143115, 32961316). 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 likely pathogenic. |
| Gene |
RCV000020499 | SCV000040949 | not provided | Glycogen storage disease, type VI | no assertion provided | literature only |