7-150945374-C-CG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000238.4(KCNH2):c.3470_3471insC(p.Ser1159GlnfsTer111) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P1157P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
KCNH2
NM_000238.4 frameshift
NM_000238.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.90
Genes affected
KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1166 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.3470_3471insC | p.Ser1159GlnfsTer111 | frameshift_variant | 15/15 | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.3470_3471insC | p.Ser1159GlnfsTer111 | frameshift_variant | 15/15 | 1 | NM_000238.4 | P1 | |
KCNH2 | ENST00000330883.9 | c.2450_2451insC | p.Ser819GlnfsTer111 | frameshift_variant | 11/11 | 1 | |||
KCNH2 | ENST00000684241.1 | n.4303_4304insC | non_coding_transcript_exon_variant | 13/13 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2018 | The c.3470dupC variant in the KCNH2 gene has been previously reported in association with LQTS and was absent from approximately 2600 control alleles (Kapplinger J et al., 2009). This variant causes a shift in reading frame starting at the final codon, changing Serine 1159 to a Glutamine, and creating an abnormal elongated protein with 110 spurious amino acids followed by a stop codon at position 111 of the new reading frame (denoted p.Ser1159GlnfsX111). Other frameshift variants in the terminal exon of the KCNH2 gene have been reported in association with LQTS. The variant is found in HERG panel(s). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at