Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001825135 | SCV002074469 | uncertain significance | not specified | 2022-01-29 | criteria provided, single submitter | clinical testing | Variant summary: PTPN11 c.329A>G (p.Glu110Gly) results in a non-conservative amino acid change located in the SH2 domain (IPR000980) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251160 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.329A>G in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two different variants at the same residue, c.328G>A (p. E110K) and c.329A>C (p.E110A) have been reported in individuals affected with or referred for genetic testing for Noonan Syndrome (HGMD database and our laboratory), suggesting that this glutamate residue is clinically significant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Fulgent Genetics, |
RCV002478072 | SCV002791093 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2022-03-30 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004536350 | SCV004116473 | likely pathogenic | PTPN11-related disorder | 2023-02-11 | criteria provided, single submitter | clinical testing | The PTPN11 c.329A>G variant is predicted to result in the amino acid substitution p.Glu110Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At PreventionGenetics, this variant has been identified in the de novo state in a fetus with valvular pulmonary stenosis. In addition, other variants impacting the p.Glu110 amino acid have been reported in individuals with Noonan syndrome (p.Glu110Ala reported as E111A, Zenker et al. 2004. PubMed ID: 15001945; p.Glu110Lys,de novo, Ezquieta et al. 2012. PubMed ID: 22465605). Taken together, this variant is interpreted as likely pathogenic. |