ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.925A>G (p.Ile309Val) (rs201787206)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000470114 SCV000616415 benign Rasopathy 2017-04-03 reviewed by expert panel curation The filtering allele frequency of the c.925A>G (p.Ile309Val) variant in the PTPN11 gene is 0.04% for European (Non-Finnish) chromosomes by the Exome Aggregation Consortium (46/66736 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1).
GeneDx RCV000589645 SCV000057424 benign not provided 2016-06-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151704 SCV000200021 benign not specified 2017-10-10 criteria provided, single submitter clinical testing p.Ile309Val in exon 8 of PTPN11: This variant is not expected to have clinical s ignificance because it has been identified in 1% (103/10152) of Ashkenazi Jewish chromosomes, including 1 homozygous individual, by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201787206). Furthermore, the p.Ile307Val variant has been identified in at least 2 unaffected individuals (Tartaglia 2002, LMM data). ACMG/AMP Criteria applied: BA1, BS2 (Richards 2015) .
Ambry Genetics RCV000252493 SCV000319157 uncertain significance Cardiovascular phenotype 2014-08-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000151704 SCV000343780 likely benign not specified 2016-07-27 criteria provided, single submitter clinical testing
Invitae RCV000589645 SCV000560644 likely benign not provided 2019-02-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589645 SCV000698087 likely benign not provided 2016-08-01 criteria provided, single submitter clinical testing Variant summary: The PTPN11 c.925A>G (p.Ile309Val) variant involves the alteration of a conserved nucleotide and affected amino acid (Ile309) is located in the Protein-tyrosine phosphatase(PTP)-like domain. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 50/121802 control chromosomes (1 homozygote) at a frequency of 0.0004105, which is approximately 7 times the estimated maximal expected allele frequency of a pathogenic PTPN11 variant (0.0000625), suggesting this variant is likely a benign polymorphism. This variant has been reported in NS patients and at least one unaffected parent, suggesting this variant may not be associated with the disease. In addition, one clinical diagnostic laboratory classified this variant as likely benign and provided following description: "this variant has been identified in 3/80 (3.8%) of Ashkenazi-Jewish control chromosomes (Dr. Bruce Gelb, LMM personal communication), suggesting that this variant is a common polymorphism in this population." Taken together, this variant is classified as likely benign.
Mendelics RCV000988916 SCV001138829 benign Metachondromatosis 2019-05-28 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761037 SCV000890952 uncertain significance Craniopharyngioma 2016-10-06 no assertion criteria provided clinical testing

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.