ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.1433A>G (p.His478Arg) (rs758131128)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478747 SCV000573808 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing The c.1433A>G variant in the PYGM gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1433A>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.1433A>G may create a cryptic splice donor site in exon 12 that could supplant the natural splice acceptor site. However, in the absence of RNA/functional studies, the actual effect of the c.1433A>G change in this individual is unknown. If c.1433A>G does not alter splicing, it will result in the H478R missense change. The H478R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret c.1433A>G as a variant of uncertain significance.

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