This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This sequence change replaces leucine with methionine at codon 84 of the ANK2 protein (p.Leu84Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ClinVar Genomic variation as it relates to human health
NM_001148.6(ANK2):c.250C>A (p.Leu84Met)
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.
(1)
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
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001148.6(ANK2):c.250C>A (p.Leu84Met)
Variation ID: 1430705 Accession: VCV001430705.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4q25 4: 113196431 (GRCh38) [ NCBI UCSC ] 4: 114117587 (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 28, 2022 Feb 28, 2024 Jul 9, 2021 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001148.6:c.250C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139.3:p.Leu84Met missense NM_001127493.3:c.187C>A NP_001120965.1:p.Leu63Met missense NM_001354225.2:c.250C>A NP_001341154.1:p.Leu84Met missense NM_001354228.2:c.250C>A NP_001341157.1:p.Leu84Met missense NM_001354230.2:c.295C>A NP_001341159.1:p.Leu99Met missense NM_001354231.2:c.295C>A NP_001341160.1:p.Leu99Met missense NM_001354232.2:c.250C>A NP_001341161.1:p.Leu84Met missense NM_001354235.2:c.250C>A NP_001341164.1:p.Leu84Met missense NM_001354236.2:c.250C>A NP_001341165.1:p.Leu84Met missense NM_001354237.2:c.295C>A NP_001341166.1:p.Leu99Met missense NM_001354239.2:c.187C>A NP_001341168.1:p.Leu63Met missense NM_001354240.2:c.295C>A NP_001341169.1:p.Leu99Met missense NM_001354241.2:c.295C>A NP_001341170.1:p.Leu99Met missense NM_001354242.2:c.295C>A NP_001341171.1:p.Leu99Met missense NM_001354243.2:c.187C>A NP_001341172.1:p.Leu63Met missense NM_001354244.2:c.187C>A NP_001341173.1:p.Leu63Met missense NM_001354245.2:c.250C>A NP_001341174.1:p.Leu84Met missense NM_001354246.2:c.250C>A NP_001341175.1:p.Leu84Met missense NM_001354249.2:c.187C>A NP_001341178.1:p.Leu63Met missense NM_001354252.2:c.187C>A NP_001341181.1:p.Leu63Met missense NM_001354253.2:c.187C>A NP_001341182.1:p.Leu63Met missense NM_001354254.2:c.187C>A NP_001341183.1:p.Leu63Met missense NM_001354255.2:c.187C>A NP_001341184.1:p.Leu63Met missense NM_001354256.2:c.187C>A NP_001341185.1:p.Leu63Met missense NM_001354257.2:c.187C>A NP_001341186.1:p.Leu63Met missense NM_001354258.2:c.250C>A NP_001341187.1:p.Leu84Met missense NM_001354260.2:c.187C>A NP_001341189.1:p.Leu63Met missense NM_001354261.2:c.232C>A NP_001341190.1:p.Leu78Met missense NM_001354262.2:c.187C>A NP_001341191.1:p.Leu63Met missense NM_001354264.2:c.187C>A NP_001341193.1:p.Leu63Met missense NM_001354265.2:c.250C>A NP_001341194.1:p.Leu84Met missense NM_001354266.2:c.187C>A NP_001341195.1:p.Leu63Met missense NM_001354267.2:c.187C>A NP_001341196.1:p.Leu63Met missense NM_001354268.2:c.250C>A NP_001341197.1:p.Leu84Met missense NM_001354269.3:c.238C>A NP_001341198.1:p.Leu80Met missense NM_001354270.2:c.187C>A NP_001341199.1:p.Leu63Met missense NM_001354271.2:c.187C>A NP_001341200.1:p.Leu63Met missense NM_001354272.2:c.187C>A NP_001341201.1:p.Leu63Met missense NM_001354273.2:c.250C>A NP_001341202.1:p.Leu84Met missense NM_001354274.2:c.187C>A NP_001341203.1:p.Leu63Met missense NM_001354275.2:c.187C>A NP_001341204.1:p.Leu63Met missense NM_001354276.2:c.187C>A NP_001341205.1:p.Leu63Met missense NM_001354277.2:c.187C>A NP_001341206.1:p.Leu63Met missense NM_001386142.1:c.187C>A NP_001373071.1:p.Leu63Met missense NM_001386143.1:c.187C>A NP_001373072.1:p.Leu63Met missense NM_001386144.1:c.295C>A NP_001373073.1:p.Leu99Met missense NM_001386146.1:c.187C>A NP_001373075.1:p.Leu63Met missense NM_001386147.1:c.232C>A NP_001373076.1:p.Leu78Met missense NM_001386148.2:c.238C>A NP_001373077.1:p.Leu80Met missense NM_001386149.1:c.187C>A NP_001373078.1:p.Leu63Met missense NM_001386150.1:c.187C>A NP_001373079.1:p.Leu63Met missense NM_001386151.1:c.187C>A NP_001373080.1:p.Leu63Met missense NM_001386152.1:c.295C>A NP_001373081.1:p.Leu99Met missense NM_001386153.1:c.187C>A NP_001373082.1:p.Leu63Met missense NM_001386154.1:c.187C>A NP_001373083.1:p.Leu63Met missense NM_001386156.1:c.187C>A NP_001373085.1:p.Leu63Met missense NM_001386157.1:c.187C>A NP_001373086.1:p.Leu63Met missense NM_001386158.1:c.187C>A NP_001373087.1:p.Leu63Met missense NM_001386160.1:c.232C>A NP_001373089.1:p.Leu78Met missense NM_001386161.1:c.187C>A NP_001373090.1:p.Leu63Met missense NM_001386162.1:c.187C>A NP_001373091.1:p.Leu63Met missense NM_001386174.1:c.301C>A NP_001373103.1:p.Leu101Met missense NM_001386175.1:c.301C>A NP_001373104.1:p.Leu101Met missense NM_001386186.2:c.238C>A NP_001373115.1:p.Leu80Met missense NM_001386187.2:c.238C>A NP_001373116.1:p.Leu80Met missense NM_020977.5:c.250C>A NP_066187.2:p.Leu84Met missense NC_000004.12:g.113196431C>A NC_000004.11:g.114117587C>A NG_009006.2:g.383349C>A LRG_327:g.383349C>A - Protein change
- L80M, L99M, L63M, L101M, L78M, L84M
- Other names
- -
- Canonical SPDI
- NC_000004.12:113196430:C: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.
- -
- 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 |
2665 | 3251 | |
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
|
Jul 9, 2021 | RCV001971898.6 |
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
(Jul 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002205285.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This sequence change replaces leucine with methionine at codon 84 … (more)
This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This sequence change replaces leucine with methionine at codon 84 of the ANK2 protein (p.Leu84Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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)
|
Comment:
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:
This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This sequence change replaces leucine with methionine at codon 84 of the ANK2 protein (p.Leu84Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
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 rs2153389915 ...
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 Sep 29, 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.