ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.1469A>G (p.Lys490Arg) (rs534760199)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481782 SCV000572979 uncertain significance not provided 2017-02-10 criteria provided, single submitter clinical testing The c.1469 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1469 A>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). Multiple in-silico splice prediction models predict that c.1469 A>G creates a cryptic splice donor site which may supplant the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.1469 A>G on splicing in this individual is unknown. If c.1469 A>G does not alter splicing, it will result in the K490R missense change. The K490R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

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