ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.175_176delinsCT (p.Ala59Leu)

dbSNP: rs727504747
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156047 SCV000205760 likely pathogenic Costello syndrome 2014-08-14 criteria provided, single submitter clinical testing The Ala59Leu variant in HRAS has now been identified in one individual with clin ical features of a Noonan spectrum disorder and was not identified in the parent s of this individual. This variant has not been previously reported in the liter ature or identified in large population studies. However, an alanine to threonin e change at the same codon in the HRAS gene has been found to segregate in three individuals within one family, all of whom reportedly have clinical features of the Noonan spectrum (LMM unpublished data). In addition, the alanine amino acid is highly conserved across evolutionarily-distinct species, and computational a nalyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) sugg est that this variant may impact the normal function of the protein. In summary, this variant is likely pathogenic, though additional studies are required to fu lly establish its clinical significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.