Table 10.

Noonan Syndrome: Notable Pathogenic Variants by Gene

Gene 1Reference SequencesDNA Nucleotide ChangePredicted
Protein Change
Comment [Reference]
PTPN11 NM_002834​.3
NP_002825​.3
c.179_181delGTGp.Gly60del Yoshida et al [2004]
c.181_183delGATp.Asp61del Lee et al [2005b]
NM_002834​.5
NP_002825​.3
c.172A>Gp.Asn58AspNS & JMML 2
c.174C>Gp.Asn58Lys
c.182A>Gp.Asp61Gly
c.184T>Gp.Tyr62Asp
c.188A>Gp.Tyr63Cys
c.214G>Ap.Ala72Thr
c.214G>Tp.Ala72Ser
c.215C>Gp.Ala72Gly
c.218C>Tp.Thr73Ile
c.227A>Tp.Glu76Val
c.228G>Tp.Glu76Asp
c.236A>Gp.Gln79Arg
c.417G>Cp.Glu139Asp
c.417G>Tp.Glu139Asp
c.794G>Ap.Arg265Gln
c.836A>Cp.Tyr279Ser
c.853T>Cp.Phe285Leu
c.922A>G 3p.Asn308Asp 3
c.923A>Gp.Asn308Ser
c.1403C>Tp.Thr468Met
c.1504T>Gp.Ser502Ala
c.1504T>Ap.Ser502Thr
c.1507G>Ap.Gly503Arg
c.1507G>Cp.Gly503Arg
c.1510A>Gp.Met504Val
RAF1 NM_002880​.4
NP_002871​.1
c.770C>Tp.Ser257Leu2 persons w/infantile fatal pulmonary hypertension 4

Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

JMML = juvenile myelomonocytic leukemia; NS = Noonan syndrome

1.

Genes from Table 1 in alphabetic order

2.

Curated from Clinvar; included variants are those classified as pathogenic or likely pathogenic with both Noonan syndrome and JMML as listed conditions for the variant [Grant et al 2018].

3.

Less likely to be associated with learning issues [Jongmans et al 2004]

4.

From: Noonan Syndrome

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