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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 853 of the ANK2 protein (p.Thr853Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline.
ClinVar Genomic variation as it relates to human health
NM_001148.6(ANK2):c.2557A>C (p.Thr853Pro)
Germline
Classification
Help
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.
(3)
Help
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
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001148.6(ANK2):c.2557A>C (p.Thr853Pro)
Variation ID: 936236 Accession: VCV000936236.7
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4q26 4: 113311263 (GRCh38) [ NCBI UCSC ] 4: 114232419 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jul 16, 2020 May 1, 2024 Jul 25, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001148.6:c.2557A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139.3:p.Thr853Pro missense NM_001127493.3:c.2494A>C NP_001120965.1:p.Thr832Pro missense NM_001354225.2:c.2557A>C NP_001341154.1:p.Thr853Pro missense NM_001354228.2:c.2557A>C NP_001341157.1:p.Thr853Pro missense NM_001354230.2:c.2602A>C NP_001341159.1:p.Thr868Pro missense NM_001354231.2:c.2602A>C NP_001341160.1:p.Thr868Pro missense NM_001354232.2:c.2557A>C NP_001341161.1:p.Thr853Pro missense NM_001354235.2:c.2557A>C NP_001341164.1:p.Thr853Pro missense NM_001354236.2:c.2557A>C NP_001341165.1:p.Thr853Pro missense NM_001354237.2:c.2602A>C NP_001341166.1:p.Thr868Pro missense NM_001354239.2:c.2494A>C NP_001341168.1:p.Thr832Pro missense NM_001354240.2:c.2602A>C NP_001341169.1:p.Thr868Pro missense NM_001354241.2:c.2602A>C NP_001341170.1:p.Thr868Pro missense NM_001354242.2:c.2602A>C NP_001341171.1:p.Thr868Pro missense NM_001354243.2:c.2494A>C NP_001341172.1:p.Thr832Pro missense NM_001354244.2:c.2494A>C NP_001341173.1:p.Thr832Pro missense NM_001354245.2:c.2458A>C NP_001341174.1:p.Thr820Pro missense NM_001354246.2:c.2557A>C NP_001341175.1:p.Thr853Pro missense NM_001354249.2:c.2470A>C NP_001341178.1:p.Thr824Pro missense NM_001354252.2:c.2494A>C NP_001341181.1:p.Thr832Pro missense NM_001354253.2:c.2395A>C NP_001341182.1:p.Thr799Pro missense NM_001354254.2:c.2494A>C NP_001341183.1:p.Thr832Pro missense NM_001354255.2:c.2494A>C NP_001341184.1:p.Thr832Pro missense NM_001354256.2:c.2494A>C NP_001341185.1:p.Thr832Pro missense NM_001354257.2:c.2395A>C NP_001341186.1:p.Thr799Pro missense NM_001354258.2:c.2557A>C NP_001341187.1:p.Thr853Pro missense NM_001354260.2:c.2371A>C NP_001341189.1:p.Thr791Pro missense NM_001354261.2:c.2515A>C NP_001341190.1:p.Thr839Pro missense NM_001354262.2:c.2494A>C NP_001341191.1:p.Thr832Pro missense NM_001354264.2:c.2470A>C NP_001341193.1:p.Thr824Pro missense NM_001354265.2:c.2557A>C NP_001341194.1:p.Thr853Pro missense NM_001354266.2:c.2470A>C NP_001341195.1:p.Thr824Pro missense NM_001354267.2:c.2470A>C NP_001341196.1:p.Thr824Pro missense NM_001354268.2:c.2458A>C NP_001341197.1:p.Thr820Pro missense NM_001354269.3:c.2347A>C NP_001341198.1:p.Thr783Pro missense NM_001354270.2:c.2395A>C NP_001341199.1:p.Thr799Pro missense NM_001354271.2:c.2371A>C NP_001341200.1:p.Thr791Pro missense NM_001354272.2:c.2494A>C NP_001341201.1:p.Thr832Pro missense NM_001354273.2:c.2359A>C NP_001341202.1:p.Thr787Pro missense NM_001354274.2:c.2470A>C NP_001341203.1:p.Thr824Pro missense NM_001354275.2:c.2494A>C NP_001341204.1:p.Thr832Pro missense NM_001354276.2:c.2470A>C NP_001341205.1:p.Thr824Pro missense NM_001354277.2:c.2272A>C NP_001341206.1:p.Thr758Pro missense NM_001354278.2:c.184A>C NP_001341207.1:p.Thr62Pro missense NM_001354279.2:c.184A>C NP_001341208.1:p.Thr62Pro missense NM_001354280.2:c.184A>C NP_001341209.1:p.Thr62Pro missense NM_001354281.2:c.184A>C NP_001341210.1:p.Thr62Pro missense NM_001354282.2:c.184A>C NP_001341211.1:p.Thr62Pro missense NM_001386142.1:c.2470A>C NP_001373071.1:p.Thr824Pro missense NM_001386143.1:c.2494A>C NP_001373072.1:p.Thr832Pro missense NM_001386144.1:c.2602A>C NP_001373073.1:p.Thr868Pro missense NM_001386146.1:c.2470A>C NP_001373075.1:p.Thr824Pro missense NM_001386147.1:c.2515A>C NP_001373076.1:p.Thr839Pro missense NM_001386148.2:c.2545A>C NP_001373077.1:p.Thr849Pro missense NM_001386149.1:c.2470A>C NP_001373078.1:p.Thr824Pro missense NM_001386150.1:c.2470A>C NP_001373079.1:p.Thr824Pro missense NM_001386151.1:c.2371A>C NP_001373080.1:p.Thr791Pro missense NM_001386152.1:c.2602A>C NP_001373081.1:p.Thr868Pro missense NM_001386153.1:c.2470A>C NP_001373082.1:p.Thr824Pro missense NM_001386154.1:c.2470A>C NP_001373083.1:p.Thr824Pro missense NM_001386156.1:c.2395A>C NP_001373085.1:p.Thr799Pro missense NM_001386157.1:c.2272A>C NP_001373086.1:p.Thr758Pro missense NM_001386158.1:c.2173A>C NP_001373087.1:p.Thr725Pro missense NM_001386160.1:c.2515A>C NP_001373089.1:p.Thr839Pro missense NM_001386161.1:c.2494A>C NP_001373090.1:p.Thr832Pro missense NM_001386162.1:c.2470A>C NP_001373091.1:p.Thr824Pro missense NM_001386174.1:c.2662A>C NP_001373103.1:p.Thr888Pro missense NM_001386175.1:c.2638A>C NP_001373104.1:p.Thr880Pro missense NM_001386186.2:c.2545A>C NP_001373115.1:p.Thr849Pro missense NM_001386187.2:c.2521A>C NP_001373116.1:p.Thr841Pro missense NM_020977.5:c.2557A>C NP_066187.2:p.Thr853Pro missense NC_000004.12:g.113311263A>C NC_000004.11:g.114232419A>C NG_009006.2:g.498181A>C LRG_327:g.498181A>C LRG_327t1:c.2557A>C - Protein change
- T758P, T853P, T868P, T62P, T783P, T799P, T839P, T787P, T791P, T824P, T832P, T820P, T725P, T841P, T849P, T880P, T888P
- Other names
- -
- Canonical SPDI
- NC_000004.12:113311262:A:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| ANK2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2690 | 3279 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2020 | RCV001204998.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 22, 2021 | RCV002504238.1 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 25, 2023 | RCV002429875.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Nov 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiac arrhythmia, ankyrin-B-related
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002815487.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Uncertain significance
(Apr 27, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001376233.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 853 of the ANK2 protein (p.Thr853Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. (less)
|
|
|
Uncertain significance
(Jul 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002742983.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2557A>C (p.T853P) alteration is located in exon 24 (coding exon 24) of the ANK2 gene. This alteration results from a A to C substitution … (more)
The c.2557A>C (p.T853P) alteration is located in exon 24 (coding exon 24) of the ANK2 gene. This alteration results from a A to C substitution at nucleotide position 2557, causing the threonine (T) at amino acid position 853 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The c.2557A>C (p.T853P) alteration is located in exon 24 (coding exon 24) of the ANK2 gene. This alteration results from a A to C substitution at nucleotide position 2557, causing the threonine (T) at amino acid position 853 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
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. |
Comment:
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ANK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 853 of the ANK2 protein (p.Thr853Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline.
Comment:
The c.2557A>C (p.T853P) alteration is located in exon 24 (coding exon 24) of the ANK2 gene. This alteration results from a A to C substitution at nucleotide position 2557, causing the threonine (T) at amino acid position 853 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| There 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 rs1178600130 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 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.