rs794728570
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000218.3(KCNQ1):āc.701A>Cā(p.Gln234Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,602 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 Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q234R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.701A>C | p.Gln234Pro | missense_variant | 5/16 | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.701A>C | p.Gln234Pro | missense_variant | 5/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000335475.6 | c.320A>C | p.Gln107Pro | missense_variant | 5/16 | 1 | |||
KCNQ1 | ENST00000496887.7 | c.440A>C | p.Gln147Pro | missense_variant | 6/16 | 5 | |||
KCNQ1 | ENST00000646564.2 | c.478-11405A>C | intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460602Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726622
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2019 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies suggest a damaging effect on channel function (Huang et al., 2018; Vanoye et al., 2018); This variant is associated with the following publications: (PMID: 27920829, 29532034, 30571187) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at