ClinVar Miner

Submissions for variant NM_004975.4(KCNB1):c.1606A>T (p.Met536Leu)

gnomAD frequency: 0.00001  dbSNP: rs1984227856
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001207638 SCV001379000 uncertain significance Developmental and epileptic encephalopathy, 26 2022-07-06 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 938424). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNB1 protein function. 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. This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 536 of the KCNB1 protein (p.Met536Leu).
GeneDx RCV001760175 SCV001991165 uncertain significance not provided 2019-02-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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