Submissions for variant NM_000218.3(KCNQ1):c.1875dup (p.Gly626fs)

dbSNP: rs2134097007

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001770709	SCV001992730	likely pathogenic	not provided	2024-03-15	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Frameshift variant predicted to result in protein truncation, as the last 51 amino acids are replaced with 25 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032853	SCV002238164	pathogenic	Long QT syndrome	2021-03-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly626Argfs*26) in the KCNQ1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the KCNQ1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNQ1-related conditions. This variant disrupts the C-terminus of the KCNQ1 protein. Other variant(s) that disrupt this region (p.Arg632Glnfs*20) have been determined to be pathogenic (PMID: 10024302, 23098067, 23631430, 25187895, 19825999, 16981927). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.