ClinVar Genomic variation as it relates to human health
NM_004119.3(FLT3):c.2503G>T (p.Asp835Tyr)
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_004119.3(FLT3):c.2503G>T (p.Asp835Tyr)
Variation ID: 16276 Accession: VCV000016276.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q12.2 13: 28018505 (GRCh38) [ NCBI UCSC ] 13: 28592642 (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 Apr 4, 2013 Apr 24, 2021 Mar 30, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004119.3:c.2503G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004110.2:p.Asp835Tyr missense NR_130706.2:n.2701G>T non-coding transcript variant NC_000013.11:g.28018505C>A NC_000013.10:g.28592642C>A NG_007066.1:g.87064G>T LRG_457:g.87064G>T P36888:p.Asp835Tyr - Protein change
- D835Y
- Other names
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- Canonical SPDI
- NC_000013.11:28018504:C: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
Help
The frequency of the allele represented by this VCV record.
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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
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
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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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FLT3 | - | - |
GRCh38 GRCh37 |
207 | 248 |
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. |
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Pathogenic (1) |
no assertion criteria provided
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May 1, 2004 | RCV000017666.4 | |
Pathogenic (3) |
no assertion criteria provided
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Mar 30, 2018 | RCV000017665.6 |
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
(May 01, 2004)
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no assertion criteria provided
Method: literature only
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LEUKEMIA, ACUTE MYELOID, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000037942.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In tumor cells derived from 22 patients with acute myeloid leukemia (601626), Yamamoto et al. (2001) found a G-to-T transition in the FLT3 gene that … (more)
In tumor cells derived from 22 patients with acute myeloid leukemia (601626), Yamamoto et al. (2001) found a G-to-T transition in the FLT3 gene that resulted in an asp835-to-tyr (D835Y) mutation. This mutation was found in compound heterozygosity with the asp835-to-glu (D835E; 136351.0006) mutation in 1 patient. Abu-Duhier et al. (2001) found that 7 of 97 cases of adult de novo acute myeloid leukemia had mutations affecting the asp835 codon of the FLT3 gene, 5 of which were D835Y. In a case of childhood hyperdiploid acute lymphoblastic leukemia (613065), Armstrong et al. (2004) identified a somatic D835Y mutation. Complete clinical remission was achieved. (less)
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Pathogenic
(May 01, 2004)
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no assertion criteria provided
Method: literature only
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LEUKEMIA, ACUTE LYMPHOBLASTIC, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000037943.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In tumor cells derived from 22 patients with acute myeloid leukemia (601626), Yamamoto et al. (2001) found a G-to-T transition in the FLT3 gene that … (more)
In tumor cells derived from 22 patients with acute myeloid leukemia (601626), Yamamoto et al. (2001) found a G-to-T transition in the FLT3 gene that resulted in an asp835-to-tyr (D835Y) mutation. This mutation was found in compound heterozygosity with the asp835-to-glu (D835E; 136351.0006) mutation in 1 patient. Abu-Duhier et al. (2001) found that 7 of 97 cases of adult de novo acute myeloid leukemia had mutations affecting the asp835 codon of the FLT3 gene, 5 of which were D835Y. In a case of childhood hyperdiploid acute lymphoblastic leukemia (613065), Armstrong et al. (2004) identified a somatic D835Y mutation. Complete clinical remission was achieved. (less)
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Pathogenic
(Oct 02, 2014)
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no assertion criteria provided
Method: literature only
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Acute myeloid leukemia
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504507.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Mar 30, 2018)
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no assertion criteria provided
Method: clinical testing
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Acute myeloid leukemia
Affected status: yes
Allele origin:
somatic
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Hematopathology, The University of Texas M.D. Anderson Cancer Center
Accession: SCV001571656.1
First in ClinVar: Apr 24, 2021 Last updated: Apr 24, 2021 |
Age: 60-69 years
Sex: female
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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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Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. | Allen C | Leukemia | 2013 | PMID: 23783394 |
The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia. | Smith CC | American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting | 2013 | PMID: 23714533 |
Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD. | Smith CC | Blood | 2013 | PMID: 23430109 |
Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. | Jourdan E | Blood | 2013 | PMID: 23321257 |
Mutational landscape of AML with normal cytogenetics: biological and clinical implications. | Martelli MP | Blood reviews | 2013 | PMID: 23261068 |
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. | Smith CC | Nature | 2012 | PMID: 22504184 |
Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. | Eisenhoffer GT | Nature | 2012 | PMID: 22504183 |
Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. | Man CH | Blood | 2012 | PMID: 22368270 |
Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. | Fischer T | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2010 | PMID: 20733134 |
Recurring mutations found by sequencing an acute myeloid leukemia genome. | Mardis ER | The New England journal of medicine | 2009 | PMID: 19657110 |
Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations. | Kancha RK | Experimental hematology | 2007 | PMID: 17889720 |
A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. | Knapper S | Blood | 2006 | PMID: 16857985 |
Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518. | Clark JJ | Blood | 2004 | PMID: 15256420 |
FLT3 mutations in childhood acute lymphoblastic leukemia. | Armstrong SA | Blood | 2004 | PMID: 14670924 |
Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. | Abu-Duhier FM | British journal of haematology | 2001 | PMID: 11442493 |
Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. | Yamamoto Y | Blood | 2001 | PMID: 11290608 |
http://docm.genome.wustl.edu/variants/ENST00000380982:c.2503G>T | - | - | - | - |
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Text-mined citations for rs121913488 ...
HelpRecord last updated Feb 13, 2023
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.