rs120074181
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PS1_Very_StrongPM1PM2PM5PP3_StrongPP5_Moderate
The NM_000218.3(KCNQ1):c.916G>A(p.Gly306Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G306V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.916G>A | p.Gly306Arg | missense_variant | 6/16 | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.916G>A | p.Gly306Arg | missense_variant | 6/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000335475.6 | c.535G>A | p.Gly179Arg | missense_variant | 6/16 | 1 | |||
KCNQ1 | ENST00000496887.7 | c.655G>A | p.Gly219Arg | missense_variant | 7/16 | 5 | |||
KCNQ1 | ENST00000646564.2 | c.478-10454G>A | intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Long QT syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1996 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2021 | Has been reported in association with LQTS in published literature (Wang et al., 1996; Kapplinger et al., 2009; Itoh et al., 2016), and in individuals referred for LQTS testing at GeneDx.; Not observed at significant frequency in large population cohorts (Lek et al., 2016); Published functional studies demonstrate G306R results in a reduction of the channel current by a dominant-negative effect (Wang et al., 1999; Li et al., 2001).; 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: 22456477, 19815527, 19716085, 11351021, 15234419, 17470695, 19490272, 26669661, 17999538, 26633542, 14678125, 25649125, 8528244, 10376919) - |
Congenital long QT syndrome Other:1
not provided, no classification provided | literature only | Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust | - | This variant has been reported as associated with Long QT syndrome in the following publications (PMID:10376919;PMID:8528244;PMID:19716085;PMID:14678125;PMID:15234419;PMID:17470695;PMID:11351021). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at