ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.4112T>C (p.Leu1371Pro)
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.4112T>C (p.Leu1371Pro)
Variation ID: 928973 Accession: VCV000928973.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51935605 (GRCh38) [ NCBI UCSC ] 13: 52509741 (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 Jun 22, 2020 Feb 14, 2024 Jun 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.4112T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Leu1371Pro missense NM_001005918.3:c.3491T>C NP_001005918.1:p.Leu1164Pro missense NM_001243182.2:c.3779T>C NP_001230111.1:p.Leu1260Pro missense NM_001330578.2:c.3878T>C NP_001317507.1:p.Leu1293Pro missense NM_001330579.2:c.3860T>C NP_001317508.1:p.Leu1287Pro missense NC_000013.11:g.51935605A>G NC_000013.10:g.52509741A>G NG_008806.1:g.80890T>C - Protein change
- L1164P, L1260P, L1287P, L1293P, L1371P
- Other names
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- Canonical SPDI
- NC_000013.11:51935604:A:G
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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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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 |
2572 | 2712 |
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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Jun 29, 2023 | RCV001193692.7 |
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
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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
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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
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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
(Aug 23, 2019)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362721.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: ATP7B c.4112T>C (p.Leu1371Pro) results in a non-conservative amino acid change located in the TM8 (Transmembrane 8) domain (Chang_2017) of the encoded protein sequence. … (more)
Variant summary: ATP7B c.4112T>C (p.Leu1371Pro) results in a non-conservative amino acid change located in the TM8 (Transmembrane 8) domain (Chang_2017) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248110 control chromosomes (gnomAD and publications). c.4112T>C has been reported in the literature in multiple individuals (compound heterozygous and heterozygous) affected with Wilson Disease (e.g. Cheng _2017, Li_2019, Panichareon_2011), particularly of Asian origin. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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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: SCV001977210.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely pathogenic
(May 05, 2022)
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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: SCV002787033.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Jun 29, 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: SCV004216387.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Jun 23, 2023)
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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: SCV003442219.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is … (more)
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1371 of the ATP7B protein (p.Leu1371Pro). This missense change has been observed in individuals with Wilson disease (PMID: 21034864, 23235335, 27022412, 29321352, 34324271, 34470610). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt ATP7B protein function. ClinVar contains an entry for this variant (Variation ID: 928973). (less)
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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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Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease. | Li M | BMC gastroenterology | 2021 | PMID: 34470610 |
Molecular analysis of 53 Chinese families with Wilson's disease: Six novel mutations identified. | Xiao Z | Molecular genetics & genomic medicine | 2021 | PMID: 34324271 |
Clinical features and mutational analysis in 114 young children with Wilson disease from South China. | Li X | American journal of medical genetics. Part A | 2019 | PMID: 31172689 |
Genetic analysis of 55 northern Vietnamese patients with Wilson disease: seven novel mutations in ATP7B. | Tuan Pham LA | Journal of genetics | 2017 | PMID: 29321352 |
The genetics of Wilson disease. | Chang IJ | Handbook of clinical neurology | 2017 | PMID: 28433102 |
Spectrum of ATP7B mutations and genotype-phenotype correlation in large-scale Chinese patients with Wilson Disease. | Cheng N | Clinical genetics | 2017 | PMID: 27982432 |
Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis. | Dong Y | Theranostics | 2016 | PMID: 27022412 |
Mutational analysis of ATP7B in north Chinese patients with Wilson disease. | Li K | Journal of human genetics | 2013 | PMID: 23235335 |
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 |
Six novel ATP7B mutations in Thai patients with Wilson disease. | Panichareon B | European journal of medical genetics | 2011 | PMID: 21034864 |
Text-mined citations for rs1444841250 ...
HelpRecord last updated Feb 14, 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.