ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.214G>C (p.Ala72Pro) (rs121918453)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000033472 SCV000927439 pathogenic not provided 2017-10-16 criteria provided, single submitter clinical testing
GeneDx RCV000033472 SCV000057377 pathogenic not provided 2013-02-04 criteria provided, single submitter clinical testing The A72P missense mutation in the PTPN11 gene has been reported previously in association with Noonan syndrome (Lee et al., 2009). In addition, other missense mutations at this codon (A72G, A72S) have been reported in association with Noonan syndrome (Tartaglia et al., 2001). The variant is found in NOONAN panel(s).
Integrated Genetics/Laboratory Corporation of America RCV000588856 SCV000698069 likely pathogenic Noonan syndrome 3 2017-01-30 criteria provided, single submitter clinical testing Variant summary: The PTPN11 c.214G>C (p.Ala72Pro) variant involves the alteration of a conserved nucleotide and is located at SH2 domain of the protein. 4/4 in silico tools predict damaging outcome for this variant. This variant is absent in 121394 control chromosomes from ExAC. PTPN11 p.Ala72Ser variant has been classified as pathogenic for NS phenotype by our laboratory and p.Ala72Thr as possibly pathogenic for JMML/ALL phenotype. Other pathogenic/potentially pathogenic variants at the same residue reported in ClinVar are p.Ala72Gly and p.Ala72Val. Thus, codon p.Ala72 is a mutational hot-spot. This variant has been reported as a germline mutation in two cases with clinical features of Noonans syndrome (Lee_2008, Hakami_2016) and as a somatic mutation in one case with acute monocytic/monoblastic leukemia (Liu_2016). Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic/likely pathogenic. Taken together, this variant is currently classified as likely pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037635 SCV000061297 likely pathogenic Noonan syndrome 2012-09-28 criteria provided, single submitter clinical testing

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