Variant Info - hg38


Gene: KCNQ1

pLI: 2.45e-05

Haploinsufficiency: 3

Transcript: NM_181798.1

Exon: 16/16

Intron: 15/15

PVS1 Flowchart

Preliminary Decision Path: DEL10
  • Deletion (single exon to full gene)
    • Single to multi exon deletion
      Preserves reading frame
      • Role of region in protein
        function is unknown #1
        • LoF variants in this exon are not frequent
          in the general population #2 and exon is
          present in biologically-relevant transcript(s)
          • Variant removes >10% of protein
            • Strong
#1 Neither mutational hotspot nor functional domain is found.
#2 Maximum LOF population frequency in exon 16 of NM_000218.3 is 3.29e-04, lower than the threshold (0.1%) we pre-defined.

Disease Mechanism

Gene Disease Clinical Validity Disease Mechanism Consideration Adjusted Strength
KCNQ1 Jervell and Lange-Nielsen syndrome Definitive No Decrease Strong
KCNQ1 short QT syndrome Strong No Decrease Strong
KCNQ1 hypertrophic cardiomyopathy No Known Disease Relationship Not applicable Unmet
KCNQ1 long QT syndrome Definitive No Decrease Strong