Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000787305 | SCV003921874 | pathogenic | Noonan syndrome 11 | 2022-02-23 | criteria provided, single submitter | clinical testing | 0101 - Gain of function is a known mechanism of disease in this gene and is associated with Noonan syndrome 11 (MIM#618499; PMID: 28289718). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional Switch II domain. This residue, and the homologous residue in other RAS proteins, is important for RAS activation; variants affecting this residue result in increased activation (PMID: 9400994). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported de novo in an individual with severe Noonan syndrome (PMID: 31173466). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed; by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| OMIM | RCV000787305 | SCV000926242 | pathogenic | Noonan syndrome 11 | 2014-12-01 | no assertion criteria provided | literature only |