ClinVar Miner

Submissions for variant NM_004975.4(KCNB1):c.1123A>G (p.Met375Val)

dbSNP: rs1984250919
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001230456 SCV001402936 pathogenic Developmental and epileptic encephalopathy, 26 2022-06-15 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 375 of the KCNB1 protein (p.Met375Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 957470). 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 expected to disrupt KCNB1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

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