ClinVar Miner

Submissions for variant NM_000293.3(PHKB):c.1090G>T (p.Glu364Ter)

gnomAD frequency: 0.00007  dbSNP: rs371296953
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779190 SCV000915720 likely pathogenic Glycogen storage disease IXb 2018-12-04 criteria provided, single submitter clinical testing The PHKB c.1090G>T (p.Glu364Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Glu364Ter variant has been reported in two studies in which it is found in two probands with phosphorylase kinase deficiency in a compound heterozygous state with another stop-gained variant (Davit-Spraul et al. 2011; Brown et al. 2015). Control data are unavailable for this variant, which is reported at a frequency of 0.000135 in the European (non-Finnish) population of the Genome Aggregation Database. Due to the potential impact of stop-gained variants and supporting evidence, the p.Glu364Ter variant is classified as likely pathogenic for phosphorylase kinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000779190 SCV002168176 pathogenic Glycogen storage disease IXb 2024-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu364*) in the PHKB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKB are known to be pathogenic (PMID: 9215682, 9326319). This variant is present in population databases (rs371296953, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 21646031). ClinVar contains an entry for this variant (Variation ID: 632256). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000779190 SCV005646902 pathogenic Glycogen storage disease IXb 2024-05-20 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004756034 SCV005361405 likely pathogenic PHKB-related disorder 2024-07-11 no assertion criteria provided clinical testing The PHKB c.1069G>T variant is predicted to result in premature protein termination (p.Glu357*). This variant has been reported in individuals with glycogen storage disease (denoted as p.R364X, Davit-Spraul et al. 2011. PubMed ID: 21646031; denoted E364X, Brown et al. 2014. PubMed ID: 25070466). This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in PHKB are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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