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NM_001754.5(RUNX1):c.596G>A (p.Gly199Glu)

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
2 (Most recent: Jan 7, 2021)
Last evaluated:
Jan 14, 2020
Accession:
VCV000869210.2
Variation ID:
869210
Description:
single nucleotide variant
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NM_001754.5(RUNX1):c.596G>A (p.Gly199Glu)

Allele ID
857422
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
21q22.12
Genomic location
21: 34859491 (GRCh38) GRCh38 UCSC
21: 36231788 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000021.8:g.36231788C>T
NC_000021.9:g.34859491C>T
NM_001754.5:c.596G>A MANE Select NP_001745.2:p.Gly199Glu missense
... more HGVS
Protein change
G172E, G199E
Other names
-
Canonical SPDI
NC_000021.9:34859490:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 reviewed by expert panel Jan 14, 2020 RCV001078217.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RUNX1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
827 890

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jan 14, 2020)
reviewed by expert panel
Method: curation
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen Myeloid Malignancy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001244326.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The NM_001754.4:c.596G>A (p.Gly199Glu) variant has been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 26884589, 25159113, 24732596; internal laboratory … (more)
Uncertain significance
(Jun 03, 2020)
criteria provided, single submitter
Method: clinical testing
Familial platelet disorder with associated myeloid malignancy
Allele origin: germline
Invitae
Accession: SCV001544669.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces glycine with glutamic acid at codon 199 of the RUNX1 protein (p.Gly199Glu). The glycine residue is highly conserved and there is … (more)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan. Yoshimi A Annals of oncology : official journal of the European Society for Medical Oncology 2016 PMID: 26884589
Recurrent CDC25C mutations drive malignant transformation in FPD/AML. Yoshimi A Nature communications 2014 PMID: 25159113
Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients. Sakurai M Leukemia 2014 PMID: 24732596
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/de750d9a-56cc-4163-b7de-f2837e11ad9b - - - -

Record last updated Aug 27, 2021