Submissions for variant NM_000218.3(KCNQ1):c.94A>T (p.Lys32Ter)

dbSNP: rs1554958043

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627202	SCV000748188	pathogenic	not provided	2018-04-02	criteria provided, single submitter	clinical testing	The K32X variant in the KCNQ1 gene has been reported previously in an individual with long QT syndrome (Chae et al., 2017). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The K32X variant is not observed in large population cohorts (Lek et al., 2016). We interpret K32X as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000631555	SCV000752637	pathogenic	Long QT syndrome	2017-08-17	criteria provided, single submitter	clinical testing	While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNQ1-related disease. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Lys32*) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product.