ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.2469dup (p.Ser824fs) (rs886041208)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000335977 SCV000329373 uncertain significance not provided 2016-08-24 criteria provided, single submitter clinical testing The c.2469dupG variant in the KCNQ3 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.2469dupG variant causes a frameshift starting with codon Serine 824, changes this amino acid to a Valine residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Ser824ValfsX14. As this frameshift variant is located in the last exon of the KCNQ3 gene, it is not expected to cause nonsense-mediated mRNA decay, however, it is predicted to cause loss of normal protein function due to an abnormal protein product. To date, only missense variants in the KCNQ3 gene have been reported in the Human Gene Mutation Database in association with epilepsy (Stenson et al., 2015), and none of them are downstream from or in the region of the c.2469dupG variant. However, the c.2469dupG variant 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. Based on review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret c.2469dupG as a variant of uncertain significance.

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