ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.4022G>A (p.Gly1341Asp)
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_000053.4(ATP7B):c.4022G>A (p.Gly1341Asp)
Variation ID: 665925 Accession: VCV000665925.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51935695 (GRCh38) [ NCBI UCSC ] 13: 52509831 (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 Aug 14, 2019 Feb 14, 2024 Jan 12, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.4022G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Gly1341Asp missense NM_001005918.3:c.3401G>A NP_001005918.1:p.Gly1134Asp missense NM_001243182.2:c.3689G>A NP_001230111.1:p.Gly1230Asp missense NM_001330578.2:c.3788G>A NP_001317507.1:p.Gly1263Asp missense NM_001330579.2:c.3770G>A NP_001317508.1:p.Gly1257Asp missense NC_000013.11:g.51935695C>T NC_000013.10:g.52509831C>T NG_008806.1:g.80800G>A - Protein change
- G1230D, G1257D, G1134D, G1263D, G1341D
- Other names
- p.Gly1341Asp
- Canonical SPDI
- NC_000013.11:51935694: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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 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 | ||
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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
Help
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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ATP7B | - | - |
GRCh38 GRCh37 |
2850 | 2991 |
Conditions - Germline
Condition
Help
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
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
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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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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 12, 2024 | RCV000824312.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 7, 2023 | RCV003480876.1 |
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. |
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Pathogenic
(Jan 12, 2024)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000965205.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1341 of the ATP7B protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1341 of the ATP7B protein (p.Gly1341Asp). This variant is present in population databases (rs779494870, gnomAD 0.003%). This missense change has been observed in individuals with Wilson disease (PMID: 16283883, 21610751, 21682854, 22484412). ClinVar contains an entry for this variant (Variation ID: 665925). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Gly1341 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been observed in individuals with ATP7B-related conditions (PMID: 14639035, 16088907, 17264425, 19937698, 21682854), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Aug 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001977216.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely pathogenic
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002800457.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004216345.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Mar 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226640.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP3, PP4, PM2, PM3_strong, PM5, PS4_moderate
Number of individuals with the variant: 1
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001455574.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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
HelpTitle | Author | Journal | Year | Link |
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ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants. | Nayagam JS | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2023 | PMID: 36096368 |
Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease. | Collins CJ | Gastroenterology | 2021 | PMID: 33640437 |
The spectrum of pathogenic variants of the ATP7B gene in Wilson disease in the Russian Federation. | Balashova MS | Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) | 2020 | PMID: 31708252 |
Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype. | Kluska A | Liver international : official journal of the International Association for the Study of the Liver | 2019 | PMID: 30230192 |
A structural model of the copper ATPase ATP7B to facilitate analysis of Wilson disease-causing mutations and studies of the transport mechanism. | Schushan M | Metallomics : integrated biometal science | 2012 | PMID: 22692182 |
Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis. | Lepori MB | Molecular and cellular probes | 2012 | PMID: 22484412 |
Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients. | Abdel Ghaffar TY | BMC pediatrics | 2011 | PMID: 21682854 |
Clinical presentation and mutations in Danish patients with Wilson disease. | Møller LB | European journal of human genetics : EJHG | 2011 | PMID: 21610751 |
Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. | van den Berghe PV | Hepatology (Baltimore, Md.) | 2009 | PMID: 19937698 |
ATP7B mutations in families in a predominantly Southern Indian cohort of Wilson's disease patients. | Santhosh S | Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology | 2006 | PMID: 17264425 |
Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. | Gromadzka G | Clinical genetics | 2005 | PMID: 16283883 |
Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. | Todorov T | Clinical genetics | 2005 | PMID: 16207219 |
Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. | Cox DW | Human mutation | 2005 | PMID: 16088907 |
A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease. | Majumdar R | European neurology | 2004 | PMID: 14639035 |
Further delineation of the molecular pathology of Wilson disease in the Mediterranean population. | Loudianos G | Human mutation | 1998 | PMID: 9671269 |
http://www.jemb.bio.uaic.ro/old_pdfs/2013/3/2013F3_05.pdf | - | - | - | - |
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Text-mined citations for rs779494870 ...
HelpRecord last updated Feb 20, 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.