Submissions for variant NM_000218.3(KCNQ1):c.878G>A (p.Arg293His)

gnomAD frequency: 0.00002  dbSNP: rs199473465

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182309	SCV000234612	likely benign	not specified	2011-08-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV001841693	SCV001347043	uncertain significance	Cardiac arrhythmia	2023-05-01	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 293 of the KCNQ1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an unaffected control individual in a long QT syndrome case-control study (PMID:19841300). This variant has been identified in 4/250276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV001258359	SCV001435326	uncertain significance	Long QT syndrome 1	2020-04-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513751	SCV003260222	uncertain significance	Long QT syndrome	2025-01-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 293 of the KCNQ1 protein (p.Arg293His). This variant is present in population databases (rs199473465, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 67118). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV002513751	SCV004838797	uncertain significance	Long QT syndrome	2023-12-01	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 293 of the KCNQ1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an unaffected control individual in a long QT syndrome case-control study (PMID:19841300). This variant has been identified in 4/250276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004019001	SCV004891497	uncertain significance	Cardiovascular phenotype	2022-01-12	criteria provided, single submitter	clinical testing	The c.878G>A (p.R293H) alteration is located in exon 6 (coding exon 6) of the KCNQ1 gene. This alteration results from a G to A substitution at nucleotide position 878, causing the arginine (R) at amino acid position 293 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057786	SCV000089305	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:19841300).