Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000037920 | SCV000061583 | likely pathogenic | Noonan syndrome | 2012-02-02 | criteria provided, single submitter | clinical testing | The Thr470Arg variant has not been reported in the literature nor previously ide ntified in over 1,400 Caucasian individuals tested by our laboratory. Since this variant was not identified in either of the parents of this individual, the var iant has likely occurred de novo, assuming that non-medical explanations includi ng alternate paternity or undisclosed adoption have been ruled out. Furthermore, this variant occurs within the functionally important G-loop of the BRAF tyrosi ne kinase domain and computational analyses (biochemical amino acid properties, conservation, PolyPhen2, SIFT, AlignGVGD) suggest that the Thr470Arg variant may impact the protein. However, this information is not predictive enough to deter mine pathogenicity. In summary, this variant is likely to be pathogenic, based o n the likely de novo occurrence of this variant in this individual. |
Gene |
RCV000681421 | SCV000808884 | likely pathogenic | not provided | 2024-09-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; This variant is associated with the following publications: (PMID: 15488754, 15520807, 16439621, 17603483, 24957944, 29493581, 18397470, 26582918) |
Service de Génétique Moléculaire, |
RCV000037920 | SCV001438446 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |