ClinVar Miner

Submissions for variant NM_000294.3(PHKG2):c.925C>T (p.Arg309Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155788 SCV003844842 likely pathogenic Glycogen phosphorylase kinase deficiency 2024-03-25 criteria provided, single submitter clinical testing Variant summary: PHKG2 c.925C>T (p.Arg309Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. In addition, this variant is located close to a splice site, therefore it can also affect splicing. Several computational tools predict a potential impact on splicing: three predict the variant weakens a canonical 5' donor site, whereas one predicts no significant impact on splicing. However, these predictions have yet to be confirmed with functional studies. The variant allele was found at a frequency of 1.2e-05 in 251028 control chromosomes (gnomAD). c.925C>T has been reported in the literature as a biallelic genotype in individuals affected with Glycogen Phosphorylase Kinase Deficiency (Glycogen Storage Disease, type IX) (e.g. Rocher_2014, Inci_2022, Wang_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. The following publications have been ascertained in the context of this evaluation (PMID: 35038814, 25266922, 35257483). ClinVar contains an entry for this variant (Variation ID: 2445869). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Breakthrough Genomics, Breakthrough Genomics RCV004596573 SCV005088906 likely pathogenic Glycogen storage disease IXc 2021-05-30 criteria provided, single submitter clinical testing This variant was previously reported in a patient with glycogen storage disease type IX. In addition, another missense variant affecting the same codon of the identified variant, p.Arg309Gln has been reported as ‘pathogenic’ in the context of Mauriac syndrome in the ClinVar database.

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