ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1742G>C (p.Arg581Pro) (rs118192235)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000992226 SCV001144317 likely pathogenic not provided 2019-06-05 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/279694 chr). Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Moderate co-segregation with disease in affected and unaffected individuals, but from a single family.
Invitae RCV001046813 SCV001210730 uncertain significance Early infantile epileptic encephalopathy 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 581 of the KCNQ2 protein (p.Arg581Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNQ2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg581 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25262651, 29186148, 25262651). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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