ClinVar Miner

Submissions for variant NM_004975.4(KCNB1):c.595A>T (p.Ile199Phe)

dbSNP: rs1601072041
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000990313 SCV001141250 likely pathogenic Developmental and epileptic encephalopathy, 26 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000990313 SCV005837959 likely pathogenic Developmental and epileptic encephalopathy, 26 2024-11-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 199 of the KCNB1 protein (p.Ile199Phe). 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 (PMID: 29264390). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 803613). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KCNB1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects KCNB1 function (PMID: 29264390). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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