Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001825053 | SCV002074159 | uncertain significance | not specified | 2022-01-09 | criteria provided, single submitter | clinical testing | Variant summary: BRAF c.1690A>G (p.Met564Val) results in a conservative amino acid change located in the Protein kinase domain (IP000719) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251270 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.1690A>G in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. 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 uncertain significance. |
Labcorp Genetics |
RCV002545197 | SCV003250253 | uncertain significance | RASopathy | 2023-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 564 of the BRAF protein (p.Met564Val). This variant is present in population databases (rs745783052, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 1339665). 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 not expected to disrupt BRAF protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Clinical Center for Gene Diagnosis and Therapy, |
RCV003319228 | SCV003932420 | likely pathogenic | Primary dilated cardiomyopathy | 2023-06-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005038347 | SCV005666112 | uncertain significance | Cardiofaciocutaneous syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7; Melanoma, cutaneous malignant, susceptibility to, 1; Colorectal cancer; Lung cancer | 2024-05-03 | criteria provided, single submitter | clinical testing |