ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.437G>A (p.Arg146Gln)

gnomAD frequency: 0.00001  dbSNP: rs557241012
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001718803 SCV000490905 likely benign not provided 2021-04-26 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29907801, 30050098)
Labcorp Genetics (formerly Invitae), Labcorp RCV000654945 SCV000776853 uncertain significance RASopathy 2024-06-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 146 of the BRAF protein (p.Arg146Gln). This variant is present in population databases (rs557241012, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of Noonan syndrome and/or related conditions (PMID: 29907801). ClinVar contains an entry for this variant (Variation ID: 372564). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BRAF function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV000764692 SCV000895824 uncertain significance Cardiofaciocutaneous syndrome 1; Lung carcinoma; Noonan syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000413361 SCV001365714 uncertain significance not specified 2020-02-25 criteria provided, single submitter clinical testing The p.Arg146Gln variant in BRAF has been reported in at least one individual with Noonan syndrome and related conditions (Leach 2018), but has also been identified in 0.02% (7/34592) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has been reported as a variant of uncertain significance in ClinVar (Variation ID 372564). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: None.
Baylor Genetics RCV001329217 SCV001520592 uncertain significance Cardiofaciocutaneous syndrome 1 2020-06-26 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago RCV000413361 SCV002061970 uncertain significance not specified 2017-10-05 criteria provided, single submitter clinical testing

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