Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome Diagnostics Laboratory, |
RCV001813335 | SCV002060708 | uncertain significance | Noonan syndrome and Noonan-related syndrome | 2021-03-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002513489 | SCV003325922 | likely pathogenic | RASopathy | 2022-03-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRAF-related conditions. 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. This variant disrupts the p.Gly596 amino acid residue in BRAF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16439621, 18413255, 19376813, 25463315). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRAF function (PMID: 28947956). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRAF protein function. ClinVar contains an entry for this variant (Variation ID: 44814). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 596 of the BRAF protein (p.Gly596Cys). |
Laboratory for Molecular Medicine, |
RCV000037933 | SCV000061598 | uncertain significance | not specified | 2016-02-11 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |