7-150950336-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000238.4(KCNH2):c.2230C>G(p.Arg744Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000238.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.2230C>G | p.Arg744Gly | missense_variant | Exon 9 of 15 | ENST00000262186.10 | NP_000229.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249862Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135478
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461218Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 726942
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74446
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1515578). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is present in population databases (rs189014161, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 744 of the KCNH2 protein (p.Arg744Gly). This variant disrupts the p.Arg744 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been observed in individuals with KCNH2-related conditions (PMID: 22314138, 26746457), which suggests that this may be a clinically significant amino acid residue. 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