Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001382416 | SCV001581170 | pathogenic | Glycogen storage disease, type V | 2022-11-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs773361937, gnomAD 0.002%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1070313). This premature translational stop signal has been observed in individual(s) with clinical features of McArdle disease (PMID: 21880526). This sequence change creates a premature translational stop signal (p.Tyr75*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001382416 | SCV002766293 | pathogenic | Glycogen storage disease, type V | 2022-11-03 | criteria provided, single submitter | clinical testing | Variant summary: PYGM c.225C>A (p.Tyr75X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. At least one truncation downstream of this position has been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250772 control chromosomes (gnomAD). c.225C>A has been reported in the literature in the compound heterozygous state together with a pathogenic variant in an individual affected with Glycogen Storage Disease, Type V (McArdle disease)(Wu_2011). Myophosphorylase activity in skeletal muscle from this patient, quantitated by glycolytic enzyme assay, was severely reduced (<1%) compared to normal, indicating the variant likely has a negative imact on protein function (Wu_2011). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Natera, |
RCV001382416 | SCV002092349 | pathogenic | Glycogen storage disease, type V | 2021-05-04 | no assertion criteria provided | clinical testing |