ClinVar Genomic variation as it relates to human health
NM_004448.4(ERBB2):c.299G>A (p.Arg100Gln)
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_004448.4(ERBB2):c.299G>A (p.Arg100Gln)
Variation ID: 2885391 Accession: VCV002885391.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 39708394 (GRCh38) [ NCBI UCSC ] 17: 37864647 (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 20, 2024 Feb 20, 2024 Dec 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004448.4:c.299G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004439.2:p.Arg100Gln missense NM_001005862.3:c.209G>A NP_001005862.1:p.Arg70Gln missense NM_001289936.2:c.254G>A NP_001276865.1:p.Arg85Gln missense NM_001289937.2:c.299G>A NP_001276866.1:p.Arg100Gln missense NM_001289938.2:c.209G>A NP_001276867.1:p.Arg70Gln missense NM_001382782.1:c.209G>A NP_001369711.1:p.Arg70Gln missense NM_001382783.1:c.209G>A NP_001369712.1:p.Arg70Gln missense NM_001382784.1:c.299G>A NP_001369713.1:p.Arg100Gln missense NM_001382785.1:c.299G>A NP_001369714.1:p.Arg100Gln missense NM_001382786.1:c.299G>A NP_001369715.1:p.Arg100Gln missense NM_001382787.1:c.299G>A NP_001369716.1:p.Arg100Gln missense NM_001382788.1:c.299G>A NP_001369717.1:p.Arg100Gln missense NM_001382789.1:c.299G>A NP_001369718.1:p.Arg100Gln missense NM_001382790.1:c.299G>A NP_001369719.1:p.Arg100Gln missense NM_001382791.1:c.290G>A NP_001369720.1:p.Arg97Gln missense NM_001382792.1:c.299G>A NP_001369721.1:p.Arg100Gln missense NM_001382793.1:c.299G>A NP_001369722.1:p.Arg100Gln missense NM_001382794.1:c.299G>A NP_001369723.1:p.Arg100Gln missense NM_001382795.1:c.299G>A NP_001369724.1:p.Arg100Gln missense NM_001382796.1:c.299G>A NP_001369725.1:p.Arg100Gln missense NM_001382797.1:c.299G>A NP_001369726.1:p.Arg100Gln missense NM_001382798.1:c.299G>A NP_001369727.1:p.Arg100Gln missense NM_001382799.1:c.299G>A NP_001369728.1:p.Arg100Gln missense NM_001382800.1:c.299G>A NP_001369729.1:p.Arg100Gln missense NM_001382801.1:c.299G>A NP_001369730.1:p.Arg100Gln missense NM_001382802.1:c.299G>A NP_001369731.1:p.Arg100Gln missense NM_001382803.1:c.299G>A NP_001369732.1:p.Arg100Gln missense NM_001382804.1:c.74-3534G>A intron variant NM_001382805.1:c.299G>A NP_001369734.1:p.Arg100Gln missense NM_001382806.1:c.299G>A NP_001369735.1:p.Arg100Gln missense NR_110535.2:n.537G>A non-coding transcript variant NC_000017.11:g.39708394G>A NC_000017.10:g.37864647G>A NG_007503.1:g.25255G>A LRG_724:g.25255G>A LRG_724t1:c.209G>A LRG_724p1:p.Arg70Gln LRG_724t2:c.299G>A LRG_724p2:p.Arg100Gln LRG_724t3:c.209G>A LRG_724p3:p.Arg70Gln LRG_724t4:c.254G>A LRG_724p4:p.Arg85Gln - Protein change
- R100Q, R97Q, R70Q, R85Q
- Other names
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- Canonical SPDI
- NC_000017.11:39708393: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.
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- 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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ERBB2 | - | - |
GRCh38 GRCh37 |
678 | 692 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Dec 28, 2023 | RCV003717241.1 |
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
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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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Uncertain significance
(Dec 28, 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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Invitae
Accession: SCV004510925.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 100 of the ERBB2 protein (p.Arg100Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 100 of the ERBB2 protein (p.Arg100Gln). This variant is present in population databases (rs756720659, gnomAD 0.01%). This missense change has been observed in individual(s) with brain metastases and/or prostate cancer (PMID: 29755676, 36095024). 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. 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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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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Whole-exome sequencing reveals a comprehensive germline mutation landscape and identifies twelve novel predisposition genes in Chinese prostate cancer patients. | Liang Y | PLoS genetics | 2022 | PMID: 36095024 |
Genetic heterogeneity and actionable mutations in HER2-positive primary breast cancers and their brain metastases. | De Mattos-Arruda L | Oncotarget | 2018 | PMID: 29755676 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 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.