Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001215821 | SCV001387584 | likely pathogenic | RASopathy | 2019-08-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 567 of the BRAF protein (p.Leu567Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual affected with BRAF-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). |
Baylor Genetics | RCV001329216 | SCV001520591 | uncertain significance | Noonan syndrome 7 | 2020-05-05 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV003222259 | SCV003918482 | likely pathogenic | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Reported in an individual with clinical features related to Noonan syndrome (Leach et al., 2019); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 29907801, 30050098) |
Service de Génétique Moléculaire, |
RCV001261047 | SCV001438449 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |