Submissions for variant NM_000218.3(KCNQ1):c.504del (p.Thr169fs)

dbSNP: rs397508114

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008071	SCV001167808	pathogenic	not provided	2020-04-09	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 10737999)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385526	SCV001585408	pathogenic	Long QT syndrome	2021-10-25	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 53054). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 10737999). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr169Argfs*68) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833).
Ambry Genetics	RCV002336181	SCV002641868	pathogenic	Cardiovascular phenotype	2019-01-01	criteria provided, single submitter	clinical testing	The c.504delG pathogenic mutation, located in coding exon 3 of the KCNQ1 gene, results from a deletion of one nucleotide at nucleotide position 504, causing a translational frameshift with a predicted alternate stop codon (p.T169Rfs*68). This alteration has been reported in patients with long QT syndrome (Wei J et al. Hum. Mutat., 2000 Apr;15:387-8; Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577363	SCV000679042	not provided	Long QT syndrome 1		no assertion provided	literature only