11-2778015-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000218.3(KCNQ1):c.1772G>T(p.Arg591Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R591C) has been classified as Pathogenic.
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461352Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727014
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Long QT syndrome 1 Pathogenic:2
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The KCNQ1 c.1772G>T (p.Arg591Leu) missense variant has been identified in individuals with long QT syndrome, found in a heterozygous state (PMID: 23158531; 32383558; 34505893). This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant is located in a known hotspot (PMID: 34505893). Another variant at the same nucleotide and amino acid position, c.1772G>A (p.Arg591His) has been reported in individuals with phenotypes consistent with long QT syndrome (PMID: 34505893). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. Based on the available evidence, the c.1772G>T (p.Arg591Leu) variant is classified as pathogenic for long QT syndrome. -
not provided Pathogenic:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23158531, 34691145, 32383558, 34505893, 35537032) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at