ClinVar Genomic variation as it relates to human health
NM_000218.3(KCNQ1):c.153C>G (p.Tyr51Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000218.3(KCNQ1):c.153C>G (p.Tyr51Ter)
Variation ID: 52989 Accession: VCV000052989.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.5 11: 2445251 (GRCh38) [ NCBI UCSC ] 11: 2466481 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 8, 2017 Apr 20, 2024 Nov 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000218.3:c.153C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000209.2:p.Tyr51Ter nonsense NC_000011.10:g.2445251C>G NC_000011.9:g.2466481C>G NG_008935.1:g.5261C>G LRG_287:g.5261C>G LRG_287t1:c.153C>G LRG_287p1:p.Tyr51Ter - Protein change
- Y51*
- Other names
- p.Y51*:TAC>TAG
- Canonical SPDI
- NC_000011.10:2445250:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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KCNQ1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
1696 | 2580 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Oct 28, 2023 | RCV000045993.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 4, 2018 | RCV000182246.13 | |
Pathogenic (1) |
criteria provided, single submitter
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May 17, 2021 | RCV001841633.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 12, 2017 | RCV002399405.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Nov 14, 2023 | RCV004017347.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002705049.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.Y51* pathogenic mutation (also known as c.153C>G), located in coding exon 1 of the KCNQ1 gene, results from a C to G substitution at … (more)
The p.Y51* pathogenic mutation (also known as c.153C>G), located in coding exon 1 of the KCNQ1 gene, results from a C to G substitution at nucleotide position 153. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. This alteration has been detected in patients referred for long QT syndrome genetic testing; however, clinical details were limited (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; Tester DJ et al. Heart Rhythm, 2005 May;2:507-17). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Oct 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000074006.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr51*) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr51*) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Long QT syndrome (PMID: 15840476, 19841300). ClinVar contains an entry for this variant (Variation ID: 52989). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely Pathogenic
(Nov 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Congenital long QT syndrome
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847387.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Tyr51X variant in KCNQ1 has been reported in at least 1 individual referred for genetic testing for long QT syndrome (LQTS; Tester 2005 PMID: … (more)
The p.Tyr51X variant in KCNQ1 has been reported in at least 1 individual referred for genetic testing for long QT syndrome (LQTS; Tester 2005 PMID: 15840476, Kapplinger 2009 PMID: 19716085, Kapa 2009 PMID: 19841300) and has also been reported by other clinical laboratories in ClinVar (Variation ID 52989). It was absent from large population studies. This nonsense variant leads to a premature termination codon at position 51, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the KCNQ1 gene is an established disease mechanism in autosomal dominant long QT syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant long QT syndrome. ACMG/AMP Criteria applied: PM2_Supporting, PVS1. (less)
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Pathogenic
(Dec 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000234549.11
First in ClinVar: Jul 05, 2015 Last updated: Apr 17, 2019 |
Comment:
The Y51X pathogenic variant in the KCNQ1 gene has been reported in a patient referred for LQTS genetic testing (Tester et al., 2005). This variant … (more)
The Y51X pathogenic variant in the KCNQ1 gene has been reported in a patient referred for LQTS genetic testing (Tester et al., 2005). This variant has also been observed in several unrelated individuals referred for LQTS testing at GeneDx. The Y51X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the KCNQ1 gene have been reported in Human Gene Mutation Database in association with KCNQ1-related disorders (Stenson et al., 2014). Furthermore, the Y51X variant is not observed in large population cohorts (Lek et al., 2016). In summary, Y51X in the KCNQ1 gene is interpreted as a pathogenic variant. (less)
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Pathogenic
(May 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001623284.1
First in ClinVar: May 23, 2021 Last updated: May 23, 2021 |
Comment:
Variant summary: KCNQ1 c.153C>G (p.Tyr51X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: KCNQ1 c.153C>G (p.Tyr51X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 7752 control chromosomes. c.153C>G has been reported in the literature in at least one individual affected with Long QT Syndrome (LQTS; e.g. Tester_2005, Kappliner_2009, Kapa_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Compound and heterozygous mutations of KCNQ1 in long QT syndrome with familial history of unexplained sudden death: Identified by analysis of whole exome sequencing and predisposing genes. | Lin Y | Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc | 2020 | PMID: 31565860 |
A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report. | Nishimura M | BMC medical genetics | 2017 | PMID: 28595573 |
The genetic basis of long QT and short QT syndromes: a mutation update. | Hedley PL | Human mutation | 2009 | PMID: 19862833 |
Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. | Kapa S | Circulation | 2009 | PMID: 19841300 |
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. | Kapplinger JD | Heart rhythm | 2009 | PMID: 19716085 |
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. | Tester DJ | Heart rhythm | 2005 | PMID: 15840476 |
Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome. | Shalaby FY | Circulation | 1997 | PMID: 9323054 |
Text-mined citations for rs397508096 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.