Table 8. [HRAS Pathogenic Variants Referenced in This GeneReview]. - GeneReviews®

Reference Sequences	DNA Nucleotide Change	Predicted Protein Change	Comment [Reference]
NM_005343.2 NP_005334.1	c.34G>A	p.Gly12Ser	Pathogenic variants at the p.Gly12 amino acid site are most commonly involved in CS [Gripp et al 2006a, Gripp et al 2019]. The risk for malignant tumors is higher in persons w/Gly12Ala than p.Gly12Ser. More severe neonatal phenotypes may be assoc w/p.Gly12Ala & p.Gly12Cys (see Genotype-Phenotype Correlations).
c.34G>T	p.Gly12Cys
c.35G>C	p.Gly12Ala
c.35_36delGCinsTT	p.Gly12Val
c.35_36delGCinsAA	p.Gly12Glu
c.37G>T	p.Gly13Cys	Pathogenic variants at the p.Gly13 site are the second most commonly involved group of variants in CS [Gripp et al 2011a, Gripp et al 2019]. Persons w/p.Gly13Asp had milder phenotypes & none had malignancy [Bertola et al 2017] (see Genotype-Phenotype Correlations.)
c.38G>A	p.Gly13Asp
c.173C>T	p.Thr58Ile	May be assoc w/milder or attenuated phenotypes [Gripp et al 2008, Gripp et al 2017] (See Genotype-Phenotype Correlations.)
c.179G>T	p.Gly60Val
c.437C>T	p.Ala146Val
c.108_110dupAGA	p.Glu37dup	Two unrelated persons w/p.Glu37dup shared similar features incl very sparse hair & less coarse facial features than typical CS [Gremer et al 2010].

Reference Sequences

DNA Nucleotide Change

Predicted Protein Change

Comment [Reference]

c.34G>A

p.Gly12Ser

Pathogenic variants at the p.Gly12 amino acid site are most commonly involved in CS [Gripp et al 2006a, Gripp et al 2019]. The risk for malignant tumors is higher in persons w/Gly12Ala than p.Gly12Ser. More severe neonatal phenotypes may be assoc w/p.Gly12Ala & p.Gly12Cys (see Genotype-Phenotype Correlations).

c.34G>T

p.Gly12Cys

c.35G>C

p.Gly12Ala

c.35_36delGCinsTT

p.Gly12Val

c.35_36delGCinsAA

p.Gly12Glu

c.37G>T

p.Gly13Cys

Pathogenic variants at the p.Gly13 site are the second most commonly involved group of variants in CS [Gripp et al 2011a, Gripp et al 2019]. Persons w/p.Gly13Asp had milder phenotypes & none had malignancy [Bertola et al 2017] (see Genotype-Phenotype Correlations.)

c.38G>A

p.Gly13Asp

c.173C>T

p.Thr58Ile

May be assoc w/milder or attenuated phenotypes [Gripp et al 2008, Gripp et al 2017] (See Genotype-Phenotype Correlations.)

c.179G>T

p.Gly60Val

c.437C>T

p.Ala146Val

c.108_110dupAGA

p.Glu37dup

Two unrelated persons w/p.Glu37dup shared similar features incl very sparse hair & less coarse facial features than typical CS [Gremer et al 2010].

From: HRAS-Related Costello Syndrome

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.