ClinVar Genomic variation as it relates to human health
NM_002382.5(MAX):c.289C>T (p.Gln97Ter)
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_002382.5(MAX):c.289C>T (p.Gln97Ter)
Variation ID: 658608 Accession: VCV000658608.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q23.3 14: 65077919 (GRCh38) [ NCBI UCSC ] 14: 65544637 (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 20, 2024 Nov 20, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002382.5:c.289C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002373.3:p.Gln97Ter nonsense NM_001271069.2:c.144+15789C>T intron variant NM_001320415.2:c.15C>T NP_001307344.1:p.Ser5= synonymous NM_001407094.1:c.289C>T NP_001394023.1:p.Gln97Ter nonsense NM_001407095.1:c.262C>T NP_001394024.1:p.Gln88Ter nonsense NM_001407096.1:c.289C>T NP_001394025.1:p.Gln97Ter nonsense NM_001407097.1:c.289C>T NP_001394026.1:p.Gln97Ter nonsense NM_001407098.1:c.181C>T NP_001394027.1:p.Gln61Ter nonsense NM_001407099.1:c.262C>T NP_001394028.1:p.Gln88Ter nonsense NM_001407100.1:c.262C>T NP_001394029.1:p.Gln88Ter nonsense NM_001407101.1:c.262C>T NP_001394030.1:p.Gln88Ter nonsense NM_001407102.1:c.262C>T NP_001394031.1:p.Gln88Ter nonsense NM_001407103.1:c.289C>T NP_001394032.1:p.Gln97Ter nonsense NM_001407104.1:c.289C>T NP_001394033.1:p.Gln97Ter nonsense NM_001407105.1:c.15C>T NP_001394034.1:p.Ser5= synonymous NM_001407106.1:c.15C>T NP_001394035.1:p.Ser5= synonymous NM_001407107.1:c.15C>T NP_001394036.1:p.Ser5= synonymous NM_001407108.1:c.262C>T NP_001394037.1:p.Gln88Ter nonsense NM_001407109.1:c.262C>T NP_001394038.1:p.Gln88Ter nonsense NM_001407110.1:c.262C>T NP_001394039.1:p.Gln88Ter nonsense NM_001407111.1:c.-79C>T 5 prime UTR NM_001407112.1:c.-79C>T 5 prime UTR NM_145112.3:c.262C>T NP_660087.1:p.Gln88Ter nonsense NM_145113.3:c.289C>T NP_660088.1:p.Gln97Ter nonsense NM_197957.4:c.171+15789C>T intron variant NR_073137.2:n.413C>T non-coding transcript variant NR_176275.1:n.431C>T non-coding transcript variant NR_176278.1:n.262C>T non-coding transcript variant NR_176279.1:n.365C>T non-coding transcript variant NR_176280.1:n.431C>T non-coding transcript variant NR_176281.1:n.431C>T non-coding transcript variant NR_176282.1:n.235C>T non-coding transcript variant NC_000014.9:g.65077919G>A NC_000014.8:g.65544637G>A NG_029830.1:g.29591C>T NG_129272.1:g.617G>A LRG_530:g.29591C>T LRG_530t1:c.289C>T LRG_530p1:p.Gln97Ter - Protein change
- Q97*, Q88*, Q61*
- Other names
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- Canonical SPDI
- NC_000014.9:65077918:G:A
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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) 0.00001
- 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
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. |
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MAX | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
385 | 528 |
Conditions - Germline
Condition
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2018 | RCV000815462.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 26, 2018 | RCV000850060.2 |
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
(Jan 26, 2018)
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criteria provided, single submitter
Method: research
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
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Academic Department of Medical Genetics, University of Cambridge
Accession: SCV000992216.1
First in ClinVar: Sep 09, 2019 Last updated: Sep 09, 2019 |
Comment:
Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Clinical Features:
Pheochromocytoma (present)
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Likely pathogenic
(Nov 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pheochromocytoma-paraganglioma
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000955916.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. This variant disrupts a region of the protein in which other variant (p.Leu102Pro) have been observed in individuals with MAX-related conditions (PMID: 22452945). This suggests that this may be a clinically significant region of the MAX protein. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has been observed in an individual affected with pheochromocytomas (PMID: 29909963). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the MAX gene (p.Gln97*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acids of the MAX protein. (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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MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. | Burnichon N | Clinical cancer research : an official journal of the American Association for Cancer Research | 2012 | PMID: 22452945 |
Text-mined citations for rs1167538050 ...
HelpRecord last updated Feb 28, 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.