ClinVar Genomic variation as it relates to human health
NM_001148.6(ANK2):c.10901T>A (p.Val3634Asp)
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.
Uncertain significance(2); Benign(1); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001148.6(ANK2):c.10901T>A (p.Val3634Asp)
Variation ID: 67599 Accession: VCV000067599.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q26 4: 113365051 (GRCh38) [ NCBI UCSC ] 4: 114286207 (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 Jun 4, 2015 Oct 8, 2024 Jul 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001148.6:c.10901T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139.3:p.Val3634Asp missense NM_001127493.3:c.4619T>A NP_001120965.1:p.Val1540Asp missense NM_001354225.2:c.4658T>A NP_001341154.1:p.Val1553Asp missense NM_001354228.2:c.4547T>A NP_001341157.1:p.Val1516Asp missense NM_001354230.2:c.4625T>A NP_001341159.1:p.Val1542Asp missense NM_001354231.2:c.4688T>A NP_001341160.1:p.Val1563Asp missense NM_001354232.2:c.4682T>A NP_001341161.1:p.Val1561Asp missense NM_001354235.2:c.4643T>A NP_001341164.1:p.Val1548Asp missense NM_001354236.2:c.4544T>A NP_001341165.1:p.Val1515Asp missense NM_001354237.2:c.4724T>A NP_001341166.1:p.Val1575Asp missense NM_001354239.2:c.4616T>A NP_001341168.1:p.Val1539Asp missense NM_001354240.2:c.4691T>A NP_001341169.1:p.Val1564Asp missense NM_001354241.2:c.4691T>A NP_001341170.1:p.Val1564Asp missense NM_001354242.2:c.4688T>A NP_001341171.1:p.Val1563Asp missense NM_001354243.2:c.4583T>A NP_001341172.1:p.Val1528Asp missense NM_001354244.2:c.4580T>A NP_001341173.1:p.Val1527Asp missense NM_001354245.2:c.4484T>A NP_001341174.1:p.Val1495Asp missense NM_001354246.2:c.4643T>A NP_001341175.1:p.Val1548Asp missense NM_001354249.2:c.4460T>A NP_001341178.1:p.Val1487Asp missense NM_001354252.2:c.4616T>A NP_001341181.1:p.Val1539Asp missense NM_001354253.2:c.4421T>A NP_001341182.1:p.Val1474Asp missense NM_001354254.2:c.4595T>A NP_001341183.1:p.Val1532Asp missense NM_001354255.2:c.4583T>A NP_001341184.1:p.Val1528Asp missense NM_001354256.2:c.4580T>A NP_001341185.1:p.Val1527Asp missense NM_001354257.2:c.4385T>A NP_001341186.1:p.Val1462Asp missense NM_001354258.2:c.4547T>A NP_001341187.1:p.Val1516Asp missense NM_001354260.2:c.4361T>A NP_001341189.1:p.Val1454Asp missense NM_001354261.2:c.4505T>A NP_001341190.1:p.Val1502Asp missense NM_001354262.2:c.4484T>A NP_001341191.1:p.Val1495Asp missense NM_001354264.2:c.4481T>A NP_001341193.1:p.Val1494Asp missense NM_001354265.2:c.4643T>A NP_001341194.1:p.Val1548Asp missense NM_001354266.2:c.4460T>A NP_001341195.1:p.Val1487Asp missense NM_001354267.2:c.4460T>A NP_001341196.1:p.Val1487Asp missense NM_001354268.2:c.4448T>A NP_001341197.1:p.Val1483Asp missense NM_001354269.3:c.4433T>A NP_001341198.1:p.Val1478Asp missense NM_001354270.2:c.4421T>A NP_001341199.1:p.Val1474Asp missense NM_001354271.2:c.4361T>A NP_001341200.1:p.Val1454Asp missense NM_001354272.2:c.4517T>A NP_001341201.1:p.Val1506Asp missense NM_001354273.2:c.4346T>A NP_001341202.1:p.Val1449Asp missense NM_001354274.2:c.4412T>A NP_001341203.1:p.Val1471Asp missense NM_001354275.2:c.4484T>A NP_001341204.1:p.Val1495Asp missense NM_001354276.2:c.4460T>A NP_001341205.1:p.Val1487Asp missense NM_001354277.2:c.4262T>A NP_001341206.1:p.Val1421Asp missense NM_001354278.2:c.2174T>A NP_001341207.1:p.Val725Asp missense NM_001354279.2:c.2210T>A NP_001341208.1:p.Val737Asp missense NM_001354280.2:c.2195T>A NP_001341209.1:p.Val732Asp missense NM_001354281.2:c.2174T>A NP_001341210.1:p.Val725Asp missense NM_001354282.2:c.2210T>A NP_001341211.1:p.Val737Asp missense NM_001386142.1:c.10667T>A NP_001373071.1:p.Val3556Asp missense NM_001386143.1:c.4583T>A NP_001373072.1:p.Val1528Asp missense NM_001386144.1:c.4691T>A NP_001373073.1:p.Val1564Asp missense NM_001386146.1:c.4427T>A NP_001373075.1:p.Val1476Asp missense NM_001386147.1:c.4472T>A NP_001373076.1:p.Val1491Asp missense NM_001386148.2:c.4631T>A NP_001373077.1:p.Val1544Asp missense NM_001386149.1:c.4427T>A NP_001373078.1:p.Val1476Asp missense NM_001386150.1:c.4427T>A NP_001373079.1:p.Val1476Asp missense NM_001386151.1:c.4361T>A NP_001373080.1:p.Val1454Asp missense NM_001386152.1:c.4703T>A NP_001373081.1:p.Val1568Asp missense NM_001386153.1:c.4427T>A NP_001373082.1:p.Val1476Asp missense NM_001386154.1:c.4412T>A NP_001373083.1:p.Val1471Asp missense NM_001386156.1:c.4385T>A NP_001373085.1:p.Val1462Asp missense NM_001386157.1:c.4262T>A NP_001373086.1:p.Val1421Asp missense NM_001386158.1:c.4163T>A NP_001373087.1:p.Val1388Asp missense NM_001386160.1:c.4490T>A NP_001373089.1:p.Val1497Asp missense NM_001386161.1:c.4580T>A NP_001373090.1:p.Val1527Asp missense NM_001386162.1:c.4460T>A NP_001373091.1:p.Val1487Asp missense NM_001386166.1:c.7301T>A NP_001373095.1:p.Val2434Asp missense NM_001386167.1:c.1046T>A NP_001373096.1:p.Val349Asp missense NM_001386174.1:c.11042T>A NP_001373103.1:p.Val3681Asp missense NM_001386175.1:c.11018T>A NP_001373104.1:p.Val3673Asp missense NM_001386186.2:c.4631T>A NP_001373115.1:p.Val1544Asp missense NM_001386187.2:c.4511T>A NP_001373116.1:p.Val1504Asp missense NM_020977.5:c.4646T>A NP_066187.2:p.Val1549Asp missense NC_000004.12:g.113365051T>A NC_000004.11:g.114286207T>A NG_009006.2:g.551969T>A LRG_327:g.551969T>A LRG_327t1:c.10901T>A - Protein change
- V1540D, V3634D, V1421D, V1449D, V1502D, V1516D, V1528D, V1532D, V732D, V1474D, V1539D, V1542D, V1549D, V1563D, V1462D, V1471D, V1478D, V1483D, V1494D, V1495D, V1515D, V1527D, V1548D, V1553D, V1561D, V1454D, V1487D, V1506D, V1564D, V1575D, V725D, V737D, V1388D, V1476D, V1491D, V1497D, V1504D, V1544D, V1568D, V2434D, V349D, V3556D, V3673D, V3681D
- Other names
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- Canonical SPDI
- NC_000004.12:113365050:T:A
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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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0.00200 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00197
1000 Genomes Project 0.00200
The Genome Aggregation Database (gnomAD) 0.00200
1000 Genomes Project 30x 0.00219
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00238
Exome Aggregation Consortium (ExAC) 0.00274
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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ANK2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2661 | 3245 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Likely benign (1) |
criteria provided, single submitter
|
Dec 14, 2018 | RCV000620213.11 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2024 | RCV000589585.23 | |
Familial dilated cardiomyopathy and peripheral neuropathy
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Benign (1) |
criteria provided, single submitter
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Jun 3, 2019 | RCV000852980.9 |
Likely benign (1) |
criteria provided, single submitter
|
Jan 22, 2024 | RCV001085479.13 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 18, 2019 | RCV001256867.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001150178.12 | |
Likely benign (2) |
criteria provided, single submitter
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Jun 24, 2013 | RCV001841765.10 | |
ANK2-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
May 30, 2019 | RCV003974947.2 |
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
Help
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
Help
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
Help
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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Uncertain significance
(Nov 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
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Conduction disorder of the heart
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433359.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
|
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Likely benign
(Dec 14, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000735816.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
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Likely benign
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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Cardiac arrhythmia
Affected status: unknown
Allele origin:
unknown
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050752.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
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Number of individuals with the variant: 5
|
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Likely benign
(Mar 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697720.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
|
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Benign
(Jun 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial dilated cardiomyopathy and peripheral neuropathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995729.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 1
|
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia, ankyrin-B-related
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001311191.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
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Likely benign
(Jan 22, 2021)
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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: SCV000166983.14
First in ClinVar: Jun 23, 2014 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31920912, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31920912, 32164423, 24025405, 17242276, 27884173, 23631430, 23174487) (less)
|
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Likely benign
(Jan 22, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000218893.11
First in ClinVar: Mar 29, 2015 Last updated: Feb 14, 2024 |
|
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Likely benign
(Jul 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV003916911.12
First in ClinVar: Apr 23, 2023 Last updated: Oct 08, 2024 |
Comment:
ANK2: PM5, BP4, BS2
Number of individuals with the variant: 12
|
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Likely benign
(May 30, 2019)
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no assertion criteria provided
Method: clinical testing
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ANK2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004791815.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
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not provided
(-)
|
no classification provided
Method: literature only
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Cardiac arrhythmia
Affected status: unknown
Allele origin:
germline
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Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089864.3
First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported as associated with Cardiac arrhythmia in the following publications (PMID:17242276). This is a literature report, and does not necessarily reflect … (more)
This variant has been reported as associated with Cardiac arrhythmia in the following publications (PMID:17242276). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. (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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Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. | Ghouse J | European heart journal | 2015 | PMID: 26159999 |
New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia. | Jabbari J | Circulation. Cardiovascular genetics | 2013 | PMID: 24025405 |
Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. | Lieve KV | Genetic testing and molecular biomarkers | 2013 | PMID: 23631430 |
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. | Lopes LR | Journal of medical genetics | 2013 | PMID: 23396983 |
Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. | Mullally J | Heart rhythm | 2013 | PMID: 23174487 |
Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function. | Wang C | Proceedings of the National Academy of Sciences of the United States of America | 2012 | PMID: 22411828 |
Cardiac ankyrins in health and disease. | Hashemi SM | Journal of molecular and cellular cardiology | 2009 | PMID: 19394342 |
Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence. | Mohler PJ | PloS one | 2007 | PMID: 17940615 |
Mechanisms of human arrhythmia syndromes: abnormal cardiac macromolecular interactions. | Mohler PJ | Physiology (Bethesda, Md.) | 2007 | PMID: 17928548 |
Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. | Mohler PJ | Circulation | 2007 | PMID: 17242276 |
Cardiac ankyrins: Essential components for development and maintenance of excitable membrane domains in heart. | Cunha SR | Cardiovascular research | 2006 | PMID: 16650839 |
Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects. | Sherman J | Heart rhythm | 2005 | PMID: 16253912 |
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Text-mined citations for rs66785829 ...
HelpRecord last updated Oct 13, 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.