rs199473443
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000218.3(KCNQ1):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,100,404 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.19C>T | p.Pro7Ser | missense_variant | Exon 1 of 16 | ENST00000155840.12 | NP_000209.2 | |
KCNQ1 | NM_001406836.1 | c.19C>T | p.Pro7Ser | missense_variant | Exon 1 of 15 | NP_001393765.1 | ||
KCNQ1 | NM_001406838.1 | c.19C>T | p.Pro7Ser | missense_variant | Exon 1 of 11 | NP_001393767.1 | ||
KCNQ1 | NM_001406837.1 | c.-344C>T | 5_prime_UTR_variant | Exon 1 of 17 | NP_001393766.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.19C>T | p.Pro7Ser | missense_variant | Exon 1 of 16 | 1 | NM_000218.3 | ENSP00000155840.2 | ||
KCNQ1 | ENST00000646564.2 | c.19C>T | p.Pro7Ser | missense_variant | Exon 1 of 11 | ENSP00000495806.2 | ||||
KCNQ1 | ENST00000496887.7 | c.24-266C>T | intron_variant | Intron 1 of 15 | 5 | ENSP00000434560.2 |
Frequencies
GnomAD3 genomes AF: 0.000182 AC: 27AN: 148034Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000356 AC: 339AN: 952262Hom.: 0 Cov.: 30 AF XY: 0.000360 AC XY: 162AN XY: 449890
GnomAD4 genome AF: 0.000176 AC: 26AN: 148142Hom.: 0 Cov.: 32 AF XY: 0.000125 AC XY: 9AN XY: 72198
ClinVar
Submissions by phenotype
not specified Uncertain:2
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant not reported in ExAC but has been reported in 1 affected individual (LQTS). In ClinVar without clinical assertion - 2 submitters (no stars). -
Variant summary: KCNQ1 c.19C>T (p.Pro7Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.19C>T has been reported in the literature in heterozygous individuals affected with autosomal dominant Long QT syndrome 1 (Johnson_2008, Thompson_2018, Yoneda_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18452873, 29790872, 34495297). ClinVar contains an entry for this variant (Variation ID: 53028). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -
not provided Uncertain:2
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KCNQ1: PS4:Moderate, PM2:Supporting, PP2, PP3 -
Long QT syndrome 1 Uncertain:1
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Beckwith-Wiedemann syndrome;C1837014:Atrial fibrillation, familial, 3;C1865019:Short QT syndrome type 2;C4551509:Jervell and Lange-Nielsen syndrome 1;C4551647:Long QT syndrome 1 Uncertain:1
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Cardiovascular phenotype Uncertain:1
The c.19C>T (p.P7S) alteration is located in exon 1 (coding exon 1) of the KCNQ1 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Long QT syndrome Benign:1
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Congenital long QT syndrome Other:1
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:18452873;PMID:19716085;PMID:19862833). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at