rs1060500622
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000218.3(KCNQ1):āc.38A>Gā(p.Lys13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,112,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000218.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.38A>G | p.Lys13Arg | missense_variant | 1/16 | ENST00000155840.12 | |
KCNQ1 | NM_001406836.1 | c.38A>G | p.Lys13Arg | missense_variant | 1/15 | ||
KCNQ1 | NM_001406838.1 | c.38A>G | p.Lys13Arg | missense_variant | 1/11 | ||
KCNQ1 | NM_001406837.1 | c.-325A>G | 5_prime_UTR_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.38A>G | p.Lys13Arg | missense_variant | 1/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000646564.2 | c.38A>G | p.Lys13Arg | missense_variant | 1/11 | ||||
KCNQ1 | ENST00000496887.7 | c.24-247A>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000136 AC: 2AN: 147468Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000207 AC: 2AN: 965062Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 2AN XY: 458864
GnomAD4 genome ? AF: 0.0000136 AC: 2AN: 147468Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 71798
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2021 | This sequence change replaces lysine with arginine at codon 13 of the KCNQ1 protein (p.Lys13Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of KCNQ1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 405256). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at