ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.775G>A (p.Asp259Asn) (rs777257591)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000853534 SCV000995916 likely pathogenic Benign familial neonatal seizures 1 2019-10-04 criteria provided, single submitter clinical testing
Invitae RCV001217360 SCV001389196 uncertain significance Early infantile epileptic encephalopathy 2019-09-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 259 of the KCNQ2 protein (p.Asp259Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs777257591, ExAC 0.001%). This variant has been observed to segregate with benign familial epilepsy in a family (PMID: 29215089). 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: "Benign"; Align-GVGD: "Class C0"). This variant disrupts the p.Asp259 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNQ2-related conditions (PMID: 27535030), which suggests that this may be a clinically significant amino acid residue. 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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