ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1058G>A (p.Arg353His) (rs796052645)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187896 SCV000241498 likely pathogenic not provided 2016-08-25 criteria provided, single submitter clinical testing The R353H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R353H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, this substitution occurs at a position that is highly conserved across species and other missense mutations in this region of the protein, including a different substitution at the same codon (R353G), have been reported in association with epilepsy (Richards, et al., 2004), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant; however, the possibility that it is a benign variant cannot be excluded.
GeneReviews RCV000678162 SCV000484607 pathogenic Early infantile epileptic encephalopathy 7 2016-03-31 no assertion criteria provided literature only EE (epileptic encephalopathy)

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