rs761811244
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS2_Supporting
The NM_000238.4(KCNH2):c.3185C>T(p.Thr1062Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000238.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.3185C>T | p.Thr1062Ile | missense_variant | Exon 14 of 15 | ENST00000262186.10 | NP_000229.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.3185C>T | p.Thr1062Ile | missense_variant | Exon 14 of 15 | 1 | NM_000238.4 | ENSP00000262186.5 | ||
KCNH2 | ENST00000330883.9 | c.2165C>T | p.Thr722Ile | missense_variant | Exon 10 of 11 | 1 | ENSP00000328531.4 | |||
KCNH2 | ENST00000684241.1 | n.4018C>T | non_coding_transcript_exon_variant | Exon 12 of 13 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248948Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134638
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1457476Hom.: 0 Cov.: 33 AF XY: 0.00000552 AC XY: 4AN XY: 724312
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
- -
Long QT syndrome Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1062 of the KCNH2 protein (p.Thr1062Ile). This variant is present in population databases (rs761811244, gnomAD 0.0009%). This missense change has been observed in individual(s) with long QT syndrome (PMID: 18675227). ClinVar contains an entry for this variant (Variation ID: 586073). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at