rs199472786
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000218.3(KCNQ1):c.1541T>C(p.Ile514Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I514V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000218.3 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 | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.1541T>C | p.Ile514Thr | missense_variant | 12/16 | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1541T>C | p.Ile514Thr | missense_variant | 12/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000335475.6 | c.1160T>C | p.Ile387Thr | missense_variant | 12/16 | 1 | |||
KCNQ1 | ENST00000496887.7 | c.1184T>C | p.Ile395Thr | missense_variant | 12/16 | 5 | |||
KCNQ1 | ENST00000646564.2 | c.1001T>C | p.Ile334Thr | missense_variant | 7/11 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Long QT syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues | Nov 16, 2018 | - - |
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:20960614). 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