ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1165C>T (p.Arg389Cys)

gnomAD frequency: 0.00002  dbSNP: rs397507472
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033297 SCV000057202 uncertain significance not provided 2012-04-13 criteria provided, single submitter clinical testing The R389C missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R389C missense change is a non-conservative amino acid substitution with a positively charged residue (Arg) being replaced by a neutral residue (Cys). Furthermore, the addition of a Cysteine residue may affect disulfide bonds. The NHLBI ESP Exome Variant Server reports that R389C was not observed in approximately 2,400 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. However, the residue at which this substitution occurs is not conserved in the protein or in related proteins. There have also been no other disease-causing mutations reported in nearby codons. Therefore, the R389C missense change is considered to be a variant of unknown clinical significance.The variant is found in NOONAN panel(s).
Invitae RCV002514141 SCV003213491 uncertain significance RASopathy 2022-10-21 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 40359). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. This variant is present in population databases (rs397507472, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 389 of the BRAF protein (p.Arg389Cys). 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.

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