Submissions for variant NM_001754.5(RUNX1):c.1005G>T (p.Gln335His)

gnomAD frequency: 0.00011  dbSNP: rs80314254

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000233738	SCV000965636	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-07-26	reviewed by expert panel	curation	The NM_001754.4:c.1005G>T (p.Gln335His) variant has a MAF of 0.00357 (0.357%, 15/4,206 alleles) in the East Asian subpopulation of the ExAC cohort that is >/= 0.0015 (0.15%) (BA1). This missense variant has a REVEL score 0.4. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000233738	SCV000287176	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000233738	SCV000435945	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV001818589	SCV002065031	likely benign	not specified	2018-06-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258842	SCV002535837	likely benign	Hereditary cancer-predisposing syndrome	2021-01-18	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316251	SCV004015363	likely benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003967630	SCV004781540	benign	RUNX1-related disorder	2019-10-31	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).