Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001754.5(RUNX1):c.592G>A (p.Asp198Asn)

CA410207977

3340076 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: eb5fc630-4965-4523-93d0-363dbe915adf

Approved on: 2026-10-05

Published on: 2026-10-05

HGVS expressions

NM_001754.5:c.592G>A

NM_001754.5(RUNX1):c.592G>A (p.Asp198Asn)

NC_000021.9:g.34859495C>T

CM000683.2:g.34859495C>T

NC_000021.8:g.36231792C>T

CM000683.1:g.36231792C>T

NC_000021.7:g.35153662C>T

NG_011402.2:g.1130217G>A

ENST00000675419.1:c.592G>A

ENST00000300305.7:c.592G>A

ENST00000344691.8:c.511G>A

ENST00000358356.9:c.511G>A

ENST00000399237.6:c.556G>A

ENST00000399240.5:c.511G>A

ENST00000437180.5:c.592G>A

ENST00000467577.1:n.84G>A

ENST00000482318.5:c.*182G>A

NM_001001890.2:c.511G>A

NM_001122607.1:c.511G>A

NM_001754.4:c.592G>A

NM_001001890.3:c.511G>A

NM_001122607.2:c.511G>A

Likely Pathogenic

PP3 PM1_Strong PM2_Supporting PS4_Supporting

PS2 PS1 PP1 PP4 PP2 PM6 PM5 PM3 PM4 BA1 BS2 PVS1 BS4 BS1 BP7 BP5 BP2 BP3 BP4 BP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RUNX1 Version 3.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.592G>A (p.Asp198Asn) is a missense variant which affects one of the hotspot residues (Asp198) within the RHD (amino acids 89-204; PM1_Strong). This variant has a REVEL score ≥ 0.88 (0.93) (PP3) and is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 26175287). In summary, this variant meets the criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1_Strong, PP3, PM2_Supporting, PS4_Supporting.

PP3

This missense variant has a REVEL score ≥ 0.88 (0.93) (PP3).

PM1_Strong

This variant affects the following hotspot residue within the RHD: D198 (PM1_strong).

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PS4_Supporting

This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 26175287).

PS2

This variant does not have a proven de novo occurrence in the literature.

PS1

There has not yet been a missense change resulting in the same change in protein which has been determined to be pathogenic at this amino acid residue.

PP1

Segregation data for this variant has not been reported in literature.

PP4

This rule is not applicable for MM-VCEP.

PP2

This rule is not applicable for MM-VCEP.

PM6

This variant does not have two or more (only 1 reported) assumed de novo occurrences in the literature.

PM5

PM1_strong met.

PM3

This rule is not applicable for MM-VCEP.

PM4

This variant is not an in-frame deletion/insertion.

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BS2

This rule is not applicable for MM-VCEP.

PVS1

This variant is not a null variant.

BS4

Segregation data for this variant has not been reported in literature.

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

BP3

This rule is not applicable for MM-VCEP.

BP4

This missense variant does not have a REVEL score < 0.50.

BP1

This rule is not applicable for MM-VCEP.

Curation History

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