ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.1520C>A (p.Thr507Lys) (rs886039463)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255951 SCV000322036 pathogenic not provided 2018-10-23 criteria provided, single submitter clinical testing The T507K pathogenic variant in the PTPN11 gene has been reported previously in at least two individuals who presented prenatally with features of Noonan syndrome (Lee et al., 2009; Jain Ghai et al., 2011). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T507K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Several missense variants in nearby residues (S502A, S502T, S502L, G503R, G503V, G503E, G503A, M504V, Q506P, Q510E, Q510R, Q510P, Q510H) have been reported in the Human Gene Mutation Database in association with PTPN11-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret T507K as a pathogenic variant.

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