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.580A>G (p.Lys194Glu)

CA410208003

3668347 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: e0820c5d-288d-4431-9179-0486d5120fa4

Approved on: 2026-04-29

Published on: 2026-04-29

HGVS expressions

NM_001754.5(RUNX1):c.580A>G (p.Lys194Glu)

NM_001754.5:c.580A>G

NC_000021.9:g.34859507T>C

CM000683.2:g.34859507T>C

NC_000021.8:g.36231804T>C

CM000683.1:g.36231804T>C

NC_000021.7:g.35153674T>C

NG_011402.2:g.1130205A>G

ENST00000675419.1:c.580A>G

ENST00000300305.7:c.580A>G

ENST00000344691.8:c.499A>G

ENST00000358356.9:c.499A>G

ENST00000399237.6:c.544A>G

ENST00000399240.5:c.499A>G

ENST00000437180.5:c.580A>G

ENST00000467577.1:n.72A>G

ENST00000482318.5:c.*170A>G

NM_001001890.2:c.499A>G

NM_001122607.1:c.499A>G

NM_001754.4:c.580A>G

NM_001001890.3:c.499A>G

NM_001122607.2:c.499A>G

Likely Pathogenic

PM2_Supporting PP3 PM1_Strong

PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP2 PM6 PM3 PM4 PM5

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 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.580A>G (p.Lys194Glu) is a missense variant which affects one of the hotspot residues (K194) in the RHD (PM1_strong). This variant has a REVEL score ≥ 0.88 (0.956) (PP3) and is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets 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.

PM2_Supporting

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

PP3

This missense variant has a REVEL score ≥ 0.88 (0.956) (PP3).

PM1_Strong

This variant affects at least one of the following hotspot residues within the RHD: K194 (PM1_strong).

PVS1

This variant is not a null variant.

BS2

This rule is not applicable for MM-VCEP

BS4

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

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS1

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

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

BP5

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

PS2

De novo data for this variant has not been reported in literature.

PS4

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

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

BA1

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

PP4

This rule is not applicable for MM-VCEP

PP1

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

PP2

This rule is not applicable for MM-VCEP

PM6

De novo data for this variant has not been reported in literature.

PM3

This rule is not applicable for MM-VCEP

PM4

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

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

Curation History

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