ClinVar Genomic variation as it relates to human health
NM_001148.6(ANK2):c.2735A>G (p.His912Arg)
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_001148.6(ANK2):c.2735A>G (p.His912Arg)
Variation ID: 978369 Accession: VCV000978369.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q26 4: 113317748 (GRCh38) [ NCBI UCSC ] 4: 114238904 (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 Sep 27, 2020 Feb 28, 2024 Oct 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001148.6:c.2735A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139.3:p.His912Arg missense NM_001127493.3:c.2672A>G NP_001120965.1:p.His891Arg missense NM_001354225.2:c.2747A>G NP_001341154.1:p.His916Arg missense NM_001354228.2:c.2735A>G NP_001341157.1:p.His912Arg missense NM_001354230.2:c.2777A>G NP_001341159.1:p.His926Arg missense NM_001354231.2:c.2777A>G NP_001341160.1:p.His926Arg missense NM_001354232.2:c.2735A>G NP_001341161.1:p.His912Arg missense NM_001354235.2:c.2732A>G NP_001341164.1:p.His911Arg missense NM_001354236.2:c.2732A>G NP_001341165.1:p.His911Arg missense NM_001354237.2:c.2777A>G NP_001341166.1:p.His926Arg missense NM_001354239.2:c.2669A>G NP_001341168.1:p.His890Arg missense NM_001354240.2:c.2780A>G NP_001341169.1:p.His927Arg missense NM_001354241.2:c.2780A>G NP_001341170.1:p.His927Arg missense NM_001354242.2:c.2777A>G NP_001341171.1:p.His926Arg missense NM_001354243.2:c.2672A>G NP_001341172.1:p.His891Arg missense NM_001354244.2:c.2669A>G NP_001341173.1:p.His890Arg missense NM_001354245.2:c.2636A>G NP_001341174.1:p.His879Arg missense NM_001354246.2:c.2732A>G NP_001341175.1:p.His911Arg missense NM_001354249.2:c.2648A>G NP_001341178.1:p.His883Arg missense NM_001354252.2:c.2669A>G NP_001341181.1:p.His890Arg missense NM_001354253.2:c.2573A>G NP_001341182.1:p.His858Arg missense NM_001354254.2:c.2684A>G NP_001341183.1:p.His895Arg missense NM_001354255.2:c.2672A>G NP_001341184.1:p.His891Arg missense NM_001354256.2:c.2669A>G NP_001341185.1:p.His890Arg missense NM_001354257.2:c.2573A>G NP_001341186.1:p.His858Arg missense NM_001354258.2:c.2735A>G NP_001341187.1:p.His912Arg missense NM_001354260.2:c.2549A>G NP_001341189.1:p.His850Arg missense NM_001354261.2:c.2693A>G NP_001341190.1:p.His898Arg missense NM_001354262.2:c.2672A>G NP_001341191.1:p.His891Arg missense NM_001354264.2:c.2648A>G NP_001341193.1:p.His883Arg missense NM_001354265.2:c.2732A>G NP_001341194.1:p.His911Arg missense NM_001354266.2:c.2648A>G NP_001341195.1:p.His883Arg missense NM_001354267.2:c.2648A>G NP_001341196.1:p.His883Arg missense NM_001354268.2:c.2636A>G NP_001341197.1:p.His879Arg missense NM_001354269.3:c.2522A>G NP_001341198.1:p.His841Arg missense NM_001354270.2:c.2573A>G NP_001341199.1:p.His858Arg missense NM_001354271.2:c.2549A>G NP_001341200.1:p.His850Arg missense NM_001354272.2:c.2669A>G NP_001341201.1:p.His890Arg missense NM_001354273.2:c.2534A>G NP_001341202.1:p.His845Arg missense NM_001354274.2:c.2633A>G NP_001341203.1:p.His878Arg missense NM_001354275.2:c.2672A>G NP_001341204.1:p.His891Arg missense NM_001354276.2:c.2648A>G NP_001341205.1:p.His883Arg missense NM_001354277.2:c.2450A>G NP_001341206.1:p.His817Arg missense NM_001354278.2:c.362A>G NP_001341207.1:p.His121Arg missense NM_001354279.2:c.362A>G NP_001341208.1:p.His121Arg missense NM_001354280.2:c.362A>G NP_001341209.1:p.His121Arg missense NM_001354281.2:c.362A>G NP_001341210.1:p.His121Arg missense NM_001354282.2:c.362A>G NP_001341211.1:p.His121Arg missense NM_001386142.1:c.2633A>G NP_001373071.1:p.His878Arg missense NM_001386143.1:c.2672A>G NP_001373072.1:p.His891Arg missense NM_001386144.1:c.2780A>G NP_001373073.1:p.His927Arg missense NM_001386146.1:c.2648A>G NP_001373075.1:p.His883Arg missense NM_001386147.1:c.2693A>G NP_001373076.1:p.His898Arg missense NM_001386148.2:c.2720A>G NP_001373077.1:p.His907Arg missense NM_001386149.1:c.2648A>G NP_001373078.1:p.His883Arg missense NM_001386150.1:c.2648A>G NP_001373079.1:p.His883Arg missense NM_001386151.1:c.2549A>G NP_001373080.1:p.His850Arg missense NM_001386152.1:c.2792A>G NP_001373081.1:p.His931Arg missense NM_001386153.1:c.2648A>G NP_001373082.1:p.His883Arg missense NM_001386154.1:c.2633A>G NP_001373083.1:p.His878Arg missense NM_001386156.1:c.2573A>G NP_001373085.1:p.His858Arg missense NM_001386157.1:c.2450A>G NP_001373086.1:p.His817Arg missense NM_001386158.1:c.2351A>G NP_001373087.1:p.His784Arg missense NM_001386160.1:c.2678A>G NP_001373089.1:p.His893Arg missense NM_001386161.1:c.2669A>G NP_001373090.1:p.His890Arg missense NM_001386162.1:c.2648A>G NP_001373091.1:p.His883Arg missense NM_001386174.1:c.2840A>G NP_001373103.1:p.His947Arg missense NM_001386175.1:c.2816A>G NP_001373104.1:p.His939Arg missense NM_001386186.2:c.2720A>G NP_001373115.1:p.His907Arg missense NM_001386187.2:c.2699A>G NP_001373116.1:p.His900Arg missense NM_020977.5:c.2735A>G NP_066187.2:p.His912Arg missense NC_000004.12:g.113317748A>G NC_000004.11:g.114238904A>G NG_009006.2:g.504666A>G LRG_327:g.504666A>G - Protein change
- H121R, H784R, H817R, H841R, H845R, H850R, H858R, H878R, H879R, H883R, H890R, H891R, H893R, H895R, H898R, H900R, H907R, H911R, H912R, H916R, H926R, H927R, H931R, H939R, H947R
- Other names
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- Canonical SPDI
- NC_000004.12:113317747:A: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
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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ANK2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2585 | 3156 |
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
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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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Uncertain significance (1) |
criteria provided, single submitter
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Jan 6, 2020 | RCV001256939.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 13, 2023 | RCV003770336.1 |
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
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
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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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Uncertain significance
(Jan 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Conduction disorder of the heart
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433460.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
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Uncertain significance
(Oct 13, 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: SCV004629167.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 912 of the ANK2 protein (p.His912Arg). … (more)
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 912 of the ANK2 protein (p.His912Arg). This variant is present in population databases (rs139259028, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 978369). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ANK2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs139259028 ...
HelpRecord last updated Mar 05, 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.