rs199473354
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_000219.6(KCNE1):c.154G>A(p.Gly52Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000923 in 1,082,960 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G52A) has been classified as Likely benign.
Frequency
Consequence
NM_000219.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNE1 | NM_000219.6 | c.154G>A | p.Gly52Arg | missense_variant | 4/4 | ENST00000399286.3 | NP_000210.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNE1 | ENST00000399286.3 | c.154G>A | p.Gly52Arg | missense_variant | 4/4 | 1 | NM_000219.6 | ENSP00000382226 | P1 |
Frequencies
GnomAD3 genomes Cov.: 16
GnomAD4 exome AF: 9.23e-7 AC: 1AN: 1082960Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 549692
GnomAD4 genome Cov.: 16
ClinVar
Submissions by phenotype
Long QT syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2020 | This sequence change replaces glycine with arginine at codon 52 of the KCNE1 protein (p.Gly52Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect KCNE1 protein function (PMID: 14499862, 27076034, 19907016). This variant has been observed in individual(s) with long QT syndrome (PMID: 14499862). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 132654). This variant is not present in population databases (ExAC no frequency). - |
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:14499862;PMID:19907016). 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