ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1690A>G (p.Met564Val)

gnomAD frequency: 0.00001  dbSNP: rs745783052
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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 (formerly Invitae), Labcorp 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, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University RCV003319228 SCV003932420 likely pathogenic Primary dilated cardiomyopathy 2023-06-01 criteria provided, single submitter clinical testing
Fulgent Genetics, 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

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