Description
The c.1588C>T (p.Gln530*) variant of the KCNQ1 gene creates a premature termination codon that is predicted to lead to an absent or truncated protein product. This variant has been identified in heterozygous, compound heterozygous or homozygous status in numerous individuals (>20) with dominant Long QT syndrome as well as recessive Jervell and Lange-Nielsen Syndrome (PMID:10973849, 23174487, 26669661, 11530100, 15051636, 14678125, 18752142, 23392653, 25705178). Loss of function variants are known to be pathogenic for KCNQ1 (PMID: 26669661, 29532034, 23098067). In-vitro assays using Chinese Hamster Ovary cells transfected with mutant plasmid and Xenopus laevis oocyte studies suggest that this variant causes defective trafficking to the cell membrane and non-functional potassium channel (PMID: 15051636, 24912595, 25705178). Truncating variants downstream of this variant are reported in individuals with Long QT syndrome (PMID:19841300, 27871843, 19716085). This variant is found to be rare (7/251292) in the general population database (gnomAD) and interpreted as pathogenic by several submitters in the ClinVar database (ClinVar ID: 52996). Therefore, the c.1588C>T (p.Gln530*) variant in the KCNQ1 gene is classified as pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | 108544 | not provided | not provided | | 5 | not provided | not provided | not provided |