Submissions for variant NM_012282.4(KCNE5):c.55G>T (p.Glu19Ter)

gnomAD frequency: 0.00028  dbSNP: rs374389286

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705431	SCV000834428	uncertain significance	Brugada syndrome	2024-09-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu19*) in the KCNE5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the KCNE5 protein. This variant is present in population databases (rs374389286, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KCNE5-related conditions. ClinVar contains an entry for this variant (Variation ID: 581565). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001700294	SCV004167415	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	KCNE5: BS2
Clinical Genetics, Academic Medical Center	RCV001700294	SCV001925698	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001700294	SCV001962904	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004757272	SCV005351224	likely benign	KCNE5-related disorder	2024-09-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).