ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.743T>C (p.Phe248Ser) (rs1057518068)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414529 SCV000491445 likely pathogenic not provided 2016-02-10 criteria provided, single submitter clinical testing The F248S variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The F248S variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. This substitution occurs at a conserved position predicted to bewithin transmembrane segment S5 of the KCNQ2 protein, and multiple missense variants in nearby residues havebeen reported in the Human Gene Mutation Database in association with KCNQ2-related disorders (Stenson et al.,2014), supporting the functional importance of this region of the protein. In silico analysis is inconsistent in itspredictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant islikely pathogenic; however, the possibility that it is benign cannot be excluded.

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