Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000218.3(KCNQ1):c.477+9C>T

CA007191

163735 (ClinVar)

Gene: KCNQ1
Condition: long QT syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 254873cf-4270-4dae-9ede-5990b5685166
Approved on: 2025-07-01
Published on: 2025-07-02

HGVS expressions

NM_000218.3:c.477+9C>T
NM_000218.3(KCNQ1):c.477+9C>T
NC_000011.10:g.2528027C>T
CM000673.2:g.2528027C>T
NC_000011.9:g.2549257C>T
CM000673.1:g.2549257C>T
NC_000011.8:g.2505833C>T
NG_008935.1:g.88037C>T
ENST00000496887.7:c.216+9C>T
ENST00000646564.2:c.477+9C>T
ENST00000155840.12:c.477+9C>T
ENST00000335475.6:c.96+9C>T
ENST00000646564.1:c.123+9C>T
ENST00000155840.9:c.477+9C>T
ENST00000335475.5:c.96+9C>T
ENST00000496887.6:c.216+9C>T
NM_000218.2:c.477+9C>T
NM_181798.1:c.96+9C>T
More

Benign

Met criteria codes 3
BA1 BP4 BP7

Evidence Links 0

Expert Panel

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.477+9C>T is a variant in intron 2. This variant is present in gnomAD v.4.1.0 at a maximum allele frequency of 0.03492 (2612 / 74792 alleles, with 48 homozygotes) in the African/African American population, which is higher than the ClinGen Potassium Channel Arrhythmia VCEP BA1 threshold of >0.001 (BA1). The computational splicing predictor SpliceAI gives this silent variant a delta score of 0.1 for donor loss which is below the ClinGen Potassium Channel Arrhythmia VCEP BP4 threshold of <0.2 and does not strongly predict a splicing defect (BP4). This intronic variant is not located within either of the regions immediately flanking the exon (between +1 and +7 or between -1 and -21), and the conservation tool PhyloP gives this variant a score of -2.693, which is below the Potassium Channel Arrhythmia VCEP BP7 threshold of <2.0 and indicates a low level of evolutionary conservation at this site (BP7). In summary, this variant meets the criteria to be classified as benign for long QT syndrome 1 based on the ACMG/AMP criteria applied, as specified by the ClinGen Potassium Channel Arrhythmia VCEP: BA1, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 03/04/2025).
Met criteria codes
BA1
This variant is present in gnomAD v.2.1.1 at a maximum allele frequency of 0.03715, (927/24956 alleles, with 15 homozygotes) in the African/African American population, which is higher than the ClinGen Potassium Channel Arrhythmia VCEP BA1 threshold of >0.001 (BA1).
BP4
The computational splicing predictor SpliceAI gives this silent variant a delta score of 0.1 for donor loss which is below the ClinGen Potassium Channel Arrhythmia VCEP BP4 threshold of <0.2 and does not strongly predict a splicing defect (BP4).
BP7
This intronic variant is not located within either of the regions immediately flanking the exon (between +1 and +7 or between -1 and -21), and the computational splicing predictor SpliceAI gives it a delta score of 0.1 for donor loss, which is below the ClinGen Potassium Channel Arrhythmia VCEP BP7 threshold of <0.2 and does not strongly predict a splicing defect. In addition, the conservation tool PhyloP gives this variant a score of -2.693, which is below the Potassium Channel Arrhythmia VCEP BP7 threshold of <2.0 and indicates a low level of evolutionary conservation at this site (BP7).
Curation History
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