ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.227A>T (p.Glu76Val) (rs121918465)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781775 SCV000920095 pathogenic Rasopathy 2017-12-10 criteria provided, single submitter clinical testing Variant summary: The PTPN11 c.227 A>T (p.Glu76Val) variant involves the alteration of a highly conserved nucleotide. The variant is located within the N-terminal SH2 domain and mutations in this domain are leading to constitutive activation of tyrosine phosphatase and, therefore, associated with oncogenesis (Panday_2017). 4/4 in silico tools used predict a damaging outcome for this variant and constitutive activation of SHP2 was confirmed by functional studies (Li_2014). This variant is absent from 245868 control chromosomes of gnomAD dataset, however was identified as a somatic event in multiple JMML and AML patients. The codon E76 is reportedly a hot-spot mutation, frequently identified in JMML (Tartaglia_2006, Park_2012). The variant was identified as a de novo germline event in a fetal sample with a severe presentation including a 11-mm nuchal translucency, cystic hygroma, fetal hydrops, hydrothorax, and generalized skin edema (Croonen_2013). Additionally, another abnormal prenatal case with alteration of the same codon has been recently reported (Mason-Suares_2017). Taken together, this variant is classified as Pathogenic.
Blueprint Genetics RCV000788241 SCV000927291 pathogenic not provided 2017-06-12 criteria provided, single submitter clinical testing
OMIM RCV000014265 SCV000034514 pathogenic Juvenile myelomonocytic leukemia 2003-06-01 no assertion criteria provided literature only

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.