ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1166G>A (p.Arg389His) (rs577372072)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764691 SCV000895823 uncertain significance Cardiofaciocutaneous syndrome 1; Lung cancer; Noonan syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000413389 SCV000490991 uncertain significance not specified 2015-05-11 criteria provided, single submitter clinical testing To our knowledge, the R389H variant has not been published as pathogenic variant, nor has it been reported as a benign polymorphism. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R389H is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species and in-silico analysis inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In addition, a missense variant in a nearby residue (R384G) has been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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