ClinVar Genomic variation as it relates to human health
NM_001148.6(ANK2):c.229G>A (p.Val77Met)
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
-
NM_001148.6(ANK2):c.229G>A (p.Val77Met)
Variation ID: 1010772 Accession: VCV001010772.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4q25 4: 113196410 (GRCh38) [ NCBI UCSC ] 4: 114117566 (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 Mar 7, 2021 May 1, 2024 Jan 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001148.6:c.229G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139.3:p.Val77Met missense NM_001127493.3:c.166G>A NP_001120965.1:p.Val56Met missense NM_001354225.2:c.229G>A NP_001341154.1:p.Val77Met missense NM_001354228.2:c.229G>A NP_001341157.1:p.Val77Met missense NM_001354230.2:c.274G>A NP_001341159.1:p.Val92Met missense NM_001354231.2:c.274G>A NP_001341160.1:p.Val92Met missense NM_001354232.2:c.229G>A NP_001341161.1:p.Val77Met missense NM_001354235.2:c.229G>A NP_001341164.1:p.Val77Met missense NM_001354236.2:c.229G>A NP_001341165.1:p.Val77Met missense NM_001354237.2:c.274G>A NP_001341166.1:p.Val92Met missense NM_001354239.2:c.166G>A NP_001341168.1:p.Val56Met missense NM_001354240.2:c.274G>A NP_001341169.1:p.Val92Met missense NM_001354241.2:c.274G>A NP_001341170.1:p.Val92Met missense NM_001354242.2:c.274G>A NP_001341171.1:p.Val92Met missense NM_001354243.2:c.166G>A NP_001341172.1:p.Val56Met missense NM_001354244.2:c.166G>A NP_001341173.1:p.Val56Met missense NM_001354245.2:c.229G>A NP_001341174.1:p.Val77Met missense NM_001354246.2:c.229G>A NP_001341175.1:p.Val77Met missense NM_001354249.2:c.166G>A NP_001341178.1:p.Val56Met missense NM_001354252.2:c.166G>A NP_001341181.1:p.Val56Met missense NM_001354253.2:c.166G>A NP_001341182.1:p.Val56Met missense NM_001354254.2:c.166G>A NP_001341183.1:p.Val56Met missense NM_001354255.2:c.166G>A NP_001341184.1:p.Val56Met missense NM_001354256.2:c.166G>A NP_001341185.1:p.Val56Met missense NM_001354257.2:c.166G>A NP_001341186.1:p.Val56Met missense NM_001354258.2:c.229G>A NP_001341187.1:p.Val77Met missense NM_001354260.2:c.166G>A NP_001341189.1:p.Val56Met missense NM_001354261.2:c.211G>A NP_001341190.1:p.Val71Met missense NM_001354262.2:c.166G>A NP_001341191.1:p.Val56Met missense NM_001354264.2:c.166G>A NP_001341193.1:p.Val56Met missense NM_001354265.2:c.229G>A NP_001341194.1:p.Val77Met missense NM_001354266.2:c.166G>A NP_001341195.1:p.Val56Met missense NM_001354267.2:c.166G>A NP_001341196.1:p.Val56Met missense NM_001354268.2:c.229G>A NP_001341197.1:p.Val77Met missense NM_001354269.3:c.217G>A NP_001341198.1:p.Val73Met missense NM_001354270.2:c.166G>A NP_001341199.1:p.Val56Met missense NM_001354271.2:c.166G>A NP_001341200.1:p.Val56Met missense NM_001354272.2:c.166G>A NP_001341201.1:p.Val56Met missense NM_001354273.2:c.229G>A NP_001341202.1:p.Val77Met missense NM_001354274.2:c.166G>A NP_001341203.1:p.Val56Met missense NM_001354275.2:c.166G>A NP_001341204.1:p.Val56Met missense NM_001354276.2:c.166G>A NP_001341205.1:p.Val56Met missense NM_001354277.2:c.166G>A NP_001341206.1:p.Val56Met missense NM_001386142.1:c.166G>A NP_001373071.1:p.Val56Met missense NM_001386143.1:c.166G>A NP_001373072.1:p.Val56Met missense NM_001386144.1:c.274G>A NP_001373073.1:p.Val92Met missense NM_001386146.1:c.166G>A NP_001373075.1:p.Val56Met missense NM_001386147.1:c.211G>A NP_001373076.1:p.Val71Met missense NM_001386148.2:c.217G>A NP_001373077.1:p.Val73Met missense NM_001386149.1:c.166G>A NP_001373078.1:p.Val56Met missense NM_001386150.1:c.166G>A NP_001373079.1:p.Val56Met missense NM_001386151.1:c.166G>A NP_001373080.1:p.Val56Met missense NM_001386152.1:c.274G>A NP_001373081.1:p.Val92Met missense NM_001386153.1:c.166G>A NP_001373082.1:p.Val56Met missense NM_001386154.1:c.166G>A NP_001373083.1:p.Val56Met missense NM_001386156.1:c.166G>A NP_001373085.1:p.Val56Met missense NM_001386157.1:c.166G>A NP_001373086.1:p.Val56Met missense NM_001386158.1:c.166G>A NP_001373087.1:p.Val56Met missense NM_001386160.1:c.211G>A NP_001373089.1:p.Val71Met missense NM_001386161.1:c.166G>A NP_001373090.1:p.Val56Met missense NM_001386162.1:c.166G>A NP_001373091.1:p.Val56Met missense NM_001386174.1:c.280G>A NP_001373103.1:p.Val94Met missense NM_001386175.1:c.280G>A NP_001373104.1:p.Val94Met missense NM_001386186.2:c.217G>A NP_001373115.1:p.Val73Met missense NM_001386187.2:c.217G>A NP_001373116.1:p.Val73Met missense NM_020977.5:c.229G>A NP_066187.2:p.Val77Met missense NC_000004.12:g.113196410G>A NC_000004.11:g.114117566G>A NG_009006.2:g.383328G>A LRG_327:g.383328G>A LRG_327t1:c.229G>A - Protein change
- V56M, V71M, V73M, V77M, V92M, V94M
- Other names
- -
- Canonical SPDI
- NC_000004.12:113196409:G:A
-
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.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00005
- 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 |
2640 | 3223 |
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
|
Jan 1, 2024 | RCV001308456.3 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 25, 2021 | RCV002447318.2 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Aug 5, 2021 | RCV002493617.1 |
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
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
(Aug 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiac arrhythmia, ankyrin-B-related
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002788775.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Uncertain significance
(Jan 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001497907.3
First in ClinVar: Mar 07, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 77 of the ANK2 protein (p.Val77Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 77 of the ANK2 protein (p.Val77Met). This variant is present in population databases (rs776254819, gnomAD 0.008%). 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: 1010772). 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 with a negative predictive value of 80%. 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)
|
|
Uncertain significance
(Jan 25, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002734833.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.V77M variant (also known as c.229G>A), located in coding exon 3 of the ANK2 gene, results from a G to A substitution at nucleotide … (more)
The p.V77M variant (also known as c.229G>A), located in coding exon 3 of the ANK2 gene, results from a G to A substitution at nucleotide position 229. The valine at codon 77 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
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 rs776254819 ...
HelpRecord last updated May 01, 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.