17-70175923-T-C
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_000891.3(KCNJ2):c.884T>C(p.Val295Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V295M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000891.3 missense
Scores
Clinical Significance
Conservation
Publications
- Andersen-Tawil syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- short QT syndrome type 3Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- short QT syndromeInheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- familial atrial fibrillationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- catecholaminergic polymorphic ventricular tachycardiaInheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
- long QT syndromeInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Verma2015[Computational]) -
Andersen Tawil syndrome;C1865018:Short QT syndrome type 3;C3151431:Atrial fibrillation, familial, 9 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at