ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.645G>A (p.Lys215=) (rs116315896)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081315 SCV000113233 benign not specified 2012-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000081315 SCV000514329 benign not specified 2016-10-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585529 SCV000692713 uncertain significance not provided 2019-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000128552 SCV000914530 pathogenic Glycogen storage disease, type V 2019-01-09 criteria provided, single submitter clinical testing The PYGM c.645G>A (p.Lys215) missense variant has been reported in at least three studies in which it has been found in a compound heterozygous state in at least five individuals with glycogen storage disease type V (GSDV) (García-Consuegra et al. 2009; Lucia et al. 2012; García-Consuegra et al. 2016). Two of these probands were brothers and two other of the probands also carried a second PYGM variant in cis with the p.Lys215 variant. The p.Lys215 variant was absent from 200 controls, but is reported at a frequency of 0.01869 in the Iberian populations in Spain from the 1000 Genomes Project. Clinical heterogeneity is observed in probands with GSDV: some probands have mild symptoms (fatigue or poor stamina) while others have a severe, rapidly progressing form that manifests shortly after birth. While the allele frequency for this variant in the population databases seems high compared to the disease prevalence, some probands may show mild symptoms and remain undiagnosed (De Castro et al. 2015). The p.Lys215 variant was shown by RT-PCR to disrupt splicing, causing inclusion of a 91-bp intron resulting in a change to the reading frame (García-Consuegra et al. 2016). Muscle biopsy tissue from probands carrying the variant showed 5% transcript levels compared to controls (García-Consuegra et al. 2009). Based on the collective evidence, the p.Lys215 variant is classified as pathogenic for glycogen storage disease type V. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000128552 SCV001113795 benign Glycogen storage disease, type V 2019-12-31 criteria provided, single submitter clinical testing
GeneReviews RCV000128552 SCV000172197 pathogenic Glycogen storage disease, type V 2014-06-26 no assertion criteria provided literature only

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