chr11-2445295-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000218.3(KCNQ1):c.197C>T(p.Ser66Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,401,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.197C>T | p.Ser66Phe | missense_variant | Exon 1 of 16 | ENST00000155840.12 | NP_000209.2 | |
KCNQ1 | NM_001406836.1 | c.197C>T | p.Ser66Phe | missense_variant | Exon 1 of 15 | NP_001393765.1 | ||
KCNQ1 | NM_001406838.1 | c.197C>T | p.Ser66Phe | missense_variant | Exon 1 of 11 | NP_001393767.1 | ||
KCNQ1 | NM_001406837.1 | c.-166C>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.197C>T | p.Ser66Phe | missense_variant | Exon 1 of 16 | 1 | NM_000218.3 | ENSP00000155840.2 | ||
KCNQ1 | ENST00000646564.2 | c.197C>T | p.Ser66Phe | missense_variant | Exon 1 of 11 | ENSP00000495806.2 | ||||
KCNQ1 | ENST00000496887.7 | c.24-88C>T | intron_variant | Intron 1 of 15 | 5 | ENSP00000434560.2 | ||||
KCNQ1 | ENST00000345015.4 | n.-27C>T | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000266 AC: 4AN: 150588Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000320 AC: 4AN: 1250308Hom.: 0 Cov.: 31 AF XY: 0.00000326 AC XY: 2AN XY: 613288
GnomAD4 genome AF: 0.0000265 AC: 4AN: 150696Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3AN XY: 73654
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 66 of the KCNQ1 protein (p.Ser66Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of long QT syndrome (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67063). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNQ1 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 34930020). 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. -
Cardiovascular phenotype Uncertain:1
The c.197C>T (p.S66F) 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 197, causing the serine (S) at amino acid position 66 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Congenital long QT syndrome Other:1
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). 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