Submissions for variant NM_004975.4(KCNB1):c.1297C>T (p.Arg433Ter)

dbSNP: rs1064794764

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482147	SCV000569899	likely pathogenic	not provided	2023-12-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 426 amino acids are lost; This variant is associated with the following publications: (PMID: 31440721, 35982159, 35982160)
Fulgent Genetics, Fulgent Genetics	RCV000763447	SCV000894221	pathogenic	Developmental and epileptic encephalopathy, 26	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000763447	SCV000933235	likely pathogenic	Developmental and epileptic encephalopathy, 26	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg433*) in the KCNB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 426 amino acid(s) of the KCNB1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KCNB1-related disease (PMID: 35982159; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 420881). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000763447	SCV005200881	pathogenic	Developmental and epileptic encephalopathy, 26	2024-06-14	criteria provided, single submitter	clinical testing	PVS1, PM2, PM6
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein	RCV000763447	SCV001739348	pathogenic	Developmental and epileptic encephalopathy, 26	2021-05-10	no assertion criteria provided	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000763447	SCV002104269	pathogenic	Developmental and epileptic encephalopathy, 26		no assertion criteria provided	clinical testing