7-150945374-C-CG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_000238.4(KCNH2):c.3470dupC(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
Consequence
NM_000238.4 frameshift
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.3470dupC | p.Ser1159GlnfsTer111 | frameshift_variant | Exon 15 of 15 | ENST00000262186.10 | NP_000229.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.3470dupC | p.Ser1159GlnfsTer111 | frameshift_variant | Exon 15 of 15 | 1 | NM_000238.4 | ENSP00000262186.5 | ||
KCNH2 | ENST00000330883.9 | c.2450dupC | p.Ser819GlnfsTer111 | frameshift_variant | Exon 11 of 11 | 1 | ENSP00000328531.4 | |||
KCNH2 | ENST00000684241.1 | n.4303dupC | non_coding_transcript_exon_variant | Exon 13 of 13 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at