Submissions for variant NM_000219.6(KCNE1):c.227_229delinsTCTA (p.Asp76fs)

dbSNP: rs1555843898

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000509561	SCV000617228	likely pathogenic	not provided	2017-12-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19716085)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000631568	SCV000752650	pathogenic	Long QT syndrome	2022-11-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Asp76Valfs*35) in the KCNE1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the KCNE1 protein. This premature translational stop signal has been observed in individual(s) with clinical features of long QT syndrome (Invitae). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant disrupts a region of the KCNE1 protein in which other variant(s) (p.Arg98Trp) have been determined to be pathogenic (PMID: 16922724, 17341399, 19907016, 30530868). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.
GenomeConnect, ClinGen	RCV000509561	SCV000607218	not provided	not provided		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.