ClinVar Miner

Submissions for variant NM_004975.4(KCNB1):c.968C>T (p.Thr323Ile)

dbSNP: rs1569017257
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratoire de Génétique Moléculaire Institut de Recherche Necker Enfants Malades, CHU Paris - Hôpital Necker-Enfants Malades RCV000782149 SCV000920613 likely pathogenic Epileptic encephalopathy 2019-03-01 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV002274100 SCV002558979 pathogenic Neurodevelopmental delay criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005056544 SCV005697591 likely pathogenic Developmental and epileptic encephalopathy, 26 2024-03-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 323 of the KCNB1 protein (p.Thr323Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 31513310). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 633622). 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 with a positive predictive value of 80%. 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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