ClinVar Miner

Submissions for variant NM_002863.5(PYGL):c.1518G>A (p.Glu506=)

dbSNP: rs748519147
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000700937 SCV000829715 likely pathogenic Glycogen storage disease, type VI 2024-05-22 criteria provided, single submitter clinical testing This sequence change affects codon 506 of the PYGL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PYGL protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is present in population databases (rs748519147, gnomAD 0.02%). This variant has been observed in individual(s) with clinical features of glycogen storage disease type VI (PMID: 25266922; Invitae). ClinVar contains an entry for this variant (Variation ID: 578046). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
3billion, Medical Genetics RCV000700937 SCV002318864 uncertain significance Glycogen storage disease, type VI 2022-03-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000239). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SPLICEAI: 0.88>=0.8). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

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