This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 831 of the ATP7B protein (p.Val831Ile). This variant is present in population databases (rs374592960, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. 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 ATP7B 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.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.2491G>A (p.Val831Ile)
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.
(2)
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000053.4(ATP7B):c.2491G>A (p.Val831Ile)
Variation ID: 2067925 Accession: VCV002067925.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51950356 (GRCh38) [ NCBI UCSC ] 13: 52524492 (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 Feb 8, 2023 Apr 20, 2024 Dec 13, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.2491G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Val831Ile missense NM_001005918.3:c.2005G>A NP_001005918.1:p.Val669Ile missense NM_001243182.2:c.2158G>A NP_001230111.1:p.Val720Ile missense NM_001330578.2:c.2257G>A NP_001317507.1:p.Val753Ile missense NM_001330579.2:c.2239G>A NP_001317508.1:p.Val747Ile missense NM_001406511.1:c.2491G>A NP_001393440.1:p.Val831Ile missense NM_001406512.1:c.2491G>A NP_001393441.1:p.Val831Ile missense NM_001406513.1:c.2491G>A NP_001393442.1:p.Val831Ile missense NM_001406514.1:c.2458G>A NP_001393443.1:p.Val820Ile missense NM_001406515.1:c.2491G>A NP_001393444.1:p.Val831Ile missense NM_001406516.1:c.2491G>A NP_001393445.1:p.Val831Ile missense NM_001406517.1:c.2395G>A NP_001393446.1:p.Val799Ile missense NM_001406518.1:c.2395G>A NP_001393447.1:p.Val799Ile missense NM_001406519.1:c.2491G>A NP_001393448.1:p.Val831Ile missense NM_001406520.1:c.2347G>A NP_001393449.1:p.Val783Ile missense NM_001406521.1:c.2347G>A NP_001393450.1:p.Val783Ile missense NM_001406522.1:c.2347G>A NP_001393451.1:p.Val783Ile missense NM_001406523.1:c.2491G>A NP_001393452.1:p.Val831Ile missense NM_001406524.1:c.2314G>A NP_001393453.1:p.Val772Ile missense NM_001406525.1:c.2491G>A NP_001393454.1:p.Val831Ile missense NM_001406526.1:c.2491G>A NP_001393455.1:p.Val831Ile missense NM_001406527.1:c.2257G>A NP_001393456.1:p.Val753Ile missense NM_001406528.1:c.2257G>A NP_001393457.1:p.Val753Ile missense NM_001406530.1:c.2251G>A NP_001393459.1:p.Val751Ile missense NM_001406531.1:c.2239G>A NP_001393460.1:p.Val747Ile missense NM_001406532.1:c.2239G>A NP_001393461.1:p.Val747Ile missense NM_001406534.1:c.2257G>A NP_001393463.1:p.Val753Ile missense NM_001406535.1:c.2491G>A NP_001393464.1:p.Val831Ile missense NM_001406536.1:c.2161G>A NP_001393465.1:p.Val721Ile missense NM_001406537.1:c.2347G>A NP_001393466.1:p.Val783Ile missense NM_001406538.1:c.2257G>A NP_001393467.1:p.Val753Ile missense NM_001406539.1:c.2062G>A NP_001393468.1:p.Val688Ile missense NM_001406540.1:c.2239G>A NP_001393469.1:p.Val747Ile missense NM_001406541.1:c.2005G>A NP_001393470.1:p.Val669Ile missense NM_001406542.1:c.2005G>A NP_001393471.1:p.Val669Ile missense NM_001406543.1:c.2143G>A NP_001393472.1:p.Val715Ile missense NM_001406544.1:c.1909G>A NP_001393473.1:p.Val637Ile missense NM_001406545.1:c.1843G>A NP_001393474.1:p.Val615Ile missense NM_001406546.1:c.2005G>A NP_001393475.1:p.Val669Ile missense NM_001406547.1:c.1843G>A NP_001393476.1:p.Val615Ile missense NC_000013.11:g.51950356C>T NC_000013.10:g.52524492C>T NG_008806.1:g.66139G>A - Protein change
- V720I, V751I, V799I, V820I, V831I, V615I, V715I, V783I, V688I, V772I, V637I, V669I, V721I, V747I, V753I
- Other names
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- Canonical SPDI
- NC_000013.11:51950355:C:T
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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.
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- 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. |
|||
| ATP7B | - | - |
GRCh38 GRCh37 |
2918 | 3062 | |
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 (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 13, 2023 | RCV002970763.4 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Feb 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003279853.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 831 of the ATP7B protein (p.Val831Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 831 of the ATP7B protein (p.Val831Ile). This variant is present in population databases (rs374592960, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. 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 ATP7B 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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Uncertain Significance
(Dec 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004845512.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces valine with isoleucine at codon 831 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces valine with isoleucine at codon 831 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 9/280940 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 7
|
Comment:
Comment:
This missense variant replaces valine with isoleucine at codon 831 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 9/280940 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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 sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 831 of the ATP7B protein (p.Val831Ile). This variant is present in population databases (rs374592960, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. 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 ATP7B 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.
Comment:
This missense variant replaces valine with isoleucine at codon 831 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 9/280940 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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 this variant ...
HelpRecord 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.