Submissions for variant NC_000012.12:g.112450397_112450398delinsCT

dbSNP: rs397516802

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037637	SCV000061299	pathogenic	Noonan syndrome	2013-04-02	criteria provided, single submitter	clinical testing	The Thr73Leu variant in PTPN11 has previously been reported in the literature in one individual with clinical features of Noonan syndrome where it was reported to have occurred de novo (Ezquieta 2012). This variant was not identified in ei ther parent of this individual and therefore likely occurred de novo, assuming t hat non-medical explanations including alternate paternity or undisclosed adopti on have been ruled out In addition, a different amino acid change at this locati on (Thr73Ile) has previously been reported in the literature in many individuals with Noonan syndrome and Noonan syndrome with Juvenile myelomonocytic leukemia or myelodysplasia (Tartaglia 2003, Kratz 2005, Tartaglia 2006, Jongmans 2005) an d is classified as pathogenic in our laboratory. The evidence above taken togeth er supports that this variant is disease causing and responsible for Noonan synd rome and possibly Juvenile myelomonocytic leukemia or myelodysplasia in this ind ividual. In summary, this variant meets our criteria to be classified as pathoge nic (http://pcpgm.partners.org/LMM).
Genomic Medicine Lab, University of California San Francisco	RCV003996327	SCV004847130	pathogenic	Noonan syndrome 1	2023-02-14	criteria provided, single submitter	clinical testing