← Lymphatic Malformation Variant Atlas

KRAS Q61R

c.182A>G NM_004985.5 RAS-MAPK transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55498739, COSV55504296, COSV55508574

Population · gnomAD Not observed Absent from the population database, consistent with a somatic, non-inherited driver.

ClinVar Conflicting classifications of pathogenicity VCV000045115

Protein region switch II Residue 61 of KRAS. UniProt P01116

AlphaMissense likely pathogenic Pathogenicity score 0.99. Computational prediction, not clinical evidence.

Position in KRAS 6 catalogued

Reported in GSD

ISSVA subset	Allele fraction	Sources
GSD	1%	PMID32591603

Bars show the reported allele-fraction range on a 0 to 50 percent axis.

Pathway and targeted therapy

Driver of the RAS-MAPK pathway. Repurposed drugs already used in the clinic for this pathway: trametinib and other MEK inhibitors.

Open and recent trials (8 in vascular / lymphatic anomalies for trametinib)

Trametinib Treatment for Complicated Vascular Anomalies ACTIVE NOT RECRUITING NCT07072403 · PHASE1, PHASE2
24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs ACTIVE NOT RECRUITING NCT07549646 · PHASE2
Pilot Study on Trametinib for Surgical Unruptured AVMs WITHDRAWN NCT06098872 · PHASE2
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia RECRUITING NCT05849662 · PHASE1, PHASE2
TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer RECRUITING NCT02693535 · PHASE2
Pediatric Long-Term Follow-up and Rollover Study ACTIVE NOT RECRUITING NCT03975829 · PHASE4

Primary sources (1)

A somatic activating KRAS variant identified in an affected lesion of a patient with Gorham-Stout disease.
Nozawa A, Ozeki M, Niihori T, Suzui N, Miyazaki T, Aoki Y. · J Hum Genet · 2020

Mentioned in 1,249 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55498739 COSMIC COSV55504296 COSMIC COSV55508574 rs121913240 gnomAD · KRAS ClinVar · Q61R OncoKB cBioPortal · KRAS VarSome UniProt · KRAS AlphaFold · KRAS