rs199472810
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1PM1PM2PP3
The NM_000218.3(KCNQ1):c.1719C>A(p.Phe573Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd. Synonymous variant affecting the same amino acid position (i.e. F573F) has been classified as Likely benign.
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.1719C>A | p.Phe573Leu | missense_variant | 14/16 | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1719C>A | p.Phe573Leu | missense_variant | 14/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000335475.6 | c.1338C>A | p.Phe446Leu | missense_variant | 14/16 | 1 | |||
KCNQ1 | ENST00000496887.7 | c.1362C>A | p.Phe454Leu | missense_variant | 14/16 | 5 | |||
KCNQ1 | ENST00000646564.2 | c.1179C>A | p.Phe393Leu | missense_variant | 9/11 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251078Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727220
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 2021 | The c.1719C>A (p.F573L) alteration is located in exon 14 (coding exon 14) of the KCNQ1 gene. This alteration results from a C to A substitution at nucleotide position 1719, causing the phenylalanine (F) at amino acid position 573 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital long QT syndrome Other:1
not provided, no classification provided | literature only | Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust | - | This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944). 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