ClinVar Miner

Submissions for variant NM_000292.3(PHKA2):c.721A>G (p.Ile241Val)

gnomAD frequency: 0.00001  dbSNP: rs367696431
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000811096 SCV000951344 uncertain significance Glycogen storage disease IXa1 2022-09-07 criteria provided, single submitter clinical testing This variant is present in population databases (rs367696431, gnomAD 0.008%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 241 of the PHKA2 protein (p.Ile241Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 655014). This missense change has been observed in individuals with glycogen storage disease type IX (PMID: 28085675).
GeneDx RCV004812369 SCV005437456 likely pathogenic not provided 2024-06-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35905201, 28085675)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005056587 SCV005726374 uncertain significance not specified 2024-11-13 criteria provided, single submitter clinical testing Variant summary: PHKA2 c.721A>G (p.Ile241Val) results in a conservative amino acid change located in the Glycosyl hydrolases family 15 ( IPR011613) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 183175 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.721A>G has been reported in the literature in individuals affected with Glycogen storage disease type IX (Hodax_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28085675). ClinVar contains an entry for this variant (Variation ID: 655014). Based on the evidence outlined above, the variant was classified as uncertain significance.

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