Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000218.3(KCNQ1):c.160_168dup (p.Ile54_Pro56dup)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA006159

42487 (ClinVar)

Gene: KCNQ1

Condition: long QT syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3cb5e056-442b-4731-ade4-516a4d2456ed

Approved on: 2025-07-01

Published on: 2025-07-02

HGVS expressions

NM_000218.3:c.160_168dupATCGCGCCC

NM_000218.3:c.160_168dup

NM_000218.3(KCNQ1):c.160_168dup (p.Ile54_Pro56dup)

NC_000011.10:g.2445258_2445266dup

CM000673.2:g.2445258_2445266dup

NC_000011.9:g.2466488_2466496dup

CM000673.1:g.2466488_2466496dup

NC_000011.8:g.2423064_2423072dup

NG_008935.1:g.5268_5276dup

ENST00000496887.7:c.24-125_24-117dup

ENST00000646564.2:c.160_168dup

ENST00000155840.12:c.160_168dup

ENST00000155840.9:c.160_168dup

ENST00000496887.6:c.24-125_24-117dup

NM_000218.2:c.160_168dup

Likely Benign

BA1 PM4

PP1 PM3 BS4

Evidence Links 0

Expert Panel

Potassium Channel Arrhythmia VCEP

Criteria Specification Information

Criteria Specification: ClinGen Potassium Channel Arrhythmia Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for KCNQ1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Potassium Channel Arrhythmia VCEP

NM_000218.3(KCNQ1):c.160_168dup (p.Pro56_Gly57insIleAlaPro) is an in-frame insertion of nine nucleotides within a non-repeat region of KCNQ1 (PM4). This variant is present in gnomAD v.4.1.0 at a maximum allele frequency of 0.03002, with 1,854 alleles / 61,766 total alleles in the African/African American population, which is higher than the ClinGen Potassium Channel Arrhythmia VCEP BA1 threshold of >0.004 (BA1). This variant has been reported in at least one affected proband with a diagnosis of long QT syndrome, however, available reported details are not sufficiently specific for long QT syndrome 1, so the PP4 and PS4 codes are not met (PMID: 28438721). This variant has been shown to disrupt KCNQ1 function in only one patch-clamp assay, so experimental evidence is not sufficient to meet PS3_Supporting (PMID 19646991). In summary, this variant meets the criteria to be classified as likely benign for long QT syndrome 1 based on the ACMG/AMP criteria applied, as specified by the ClinGen Potassium Channel Arrhythmia VCEP: BA1 and PM4. (VCEP specifications version 1.0.0; date of approval 03/04/2025).

BA1

This variant is present in gnomAD v.4.1.0 at a maximum allele frequency of 0.03002, with 1,854 alleles / 61,766 total alleles in the African/African American population, which is higher than the ClinGen Potassium Channel Arrhythmia VCEP BA1 threshold of >0.004 (BA1).

PM4

This variant is an in-frame insertion of three codons between within a non-repeat region of KCNQ1 (PM4).

PP1

The variant has been reported to segregate with long QT syndrome 1 through the proband and 2 affected family members, but their QTc <480ms, so they can not be counted (PMID: 28438721).

PM3

This variant was observed in compound heterozygosity with a pathogenic KCNQ1 variant, c.535G>A (p.Gly179Ser), but the individual does not have congenital deafness or a diagnosis of JLNS (PMID 28438721), so this code is not applicable.

BS4

The variant has been observed in a family with long QT syndrome but fails to segregate with the disease phenotype in at least 1 affected member; however their phenotype is insufficiently specific so BS4 is not met (PMID: 28438721).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.