Submissions for variant NM_000218.3(KCNQ1):c.850_852del (p.Glu284del)

dbSNP: rs1064796353

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486506	SCV000572986	likely pathogenic	not provided	2017-02-15	criteria provided, single submitter	clinical testing	An in-frame deletion that is likely pathogenic was identified in the KCNQ1 gene. The c.850_852delGAG variant has not been published as pathogenic nor been reported as benign to our knowledge. c.850_852delGAG results in an in-frame deletion of a glutamic acid residue at position 284, denoted p.Glu284del. Multiple in-frame deletions in the KCNQ1 gene, as well as a pathogenic missense variant in this residue (E284K), have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.850_852delGAG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, c.850_852delGAG in the KCNQ1 gene is interpreted as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248259	SCV001421730	pathogenic	Long QT syndrome	2023-05-08	criteria provided, single submitter	clinical testing	This variant disrupts a region of the KCNQ1 protein in which other variant(s) (p.Glu284Lys) have been determined to be pathogenic (PMID: 14678125, 17470695; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 423306). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.850_852del, results in the deletion of 1 amino acid(s) of the KCNQ1 protein (p.Glu284del), but otherwise preserves the integrity of the reading frame.
Ambry Genetics	RCV002446944	SCV002680708	uncertain significance	Cardiovascular phenotype	2019-11-07	criteria provided, single submitter	clinical testing	The c.850_852delGAG variant (also known as p.E284del) is located in coding exon 6 of the KCNQ1 gene. This variant results from an in-frame GAG deletion at nucleotide positions 850 to 852. This results in the in-frame deletion of a glutamic acid at codon 284, and is located in the transmembrane-spanning S5/pore domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.