rs1273257287
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000218.3(KCNQ1):c.181C>A(p.Pro61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,303,178 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P61S) has been classified 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.181C>A | p.Pro61Thr | missense_variant | 1/16 | ENST00000155840.12 | |
KCNQ1 | NM_001406836.1 | c.181C>A | p.Pro61Thr | missense_variant | 1/15 | ||
KCNQ1 | NM_001406838.1 | c.181C>A | p.Pro61Thr | missense_variant | 1/11 | ||
KCNQ1 | NM_001406837.1 | c.-182C>A | 5_prime_UTR_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.181C>A | p.Pro61Thr | missense_variant | 1/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000646564.2 | c.181C>A | p.Pro61Thr | missense_variant | 1/11 | ||||
KCNQ1 | ENST00000496887.7 | c.24-104C>A | intron_variant | 5 | |||||
KCNQ1 | ENST00000345015.4 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000267 AC: 4AN: 149850Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000147 AC: 17AN: 1153328Hom.: 0 Cov.: 31 AF XY: 0.0000161 AC XY: 9AN XY: 559752
GnomAD4 genome ? AF: 0.0000267 AC: 4AN: 149850Hom.: 0 Cov.: 32 AF XY: 0.0000410 AC XY: 3AN XY: 73116
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 15, 2017 | The p.Pro61Thr variant in KCNQ1 has not been previously reported in individuals with hearing loss or long QT syndrome and was absent from large population studi es. Computational prediction tools and conservation analysis suggest that the p. Pro61Thr variant may not impact the protein, though this information is not pred ictive enough to rule out pathogenicity. In summary, the clinical significance o f the p.Pro61Thr variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2023 | The p.P61T variant (also known as c.181C>A), located in coding exon 1 of the KCNQ1 gene, results from a C to A substitution at nucleotide position 181. The proline at codon 61 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in association with long QT syndrome (Walsh R et al. Genet Med, 2021 Jan;23:47-58; Schwartz PJ et al. Eur Heart J, 2021 Dec;42:4743-4755). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at