ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.41C>G (p.Pro14Arg) (rs397507455)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033266 SCV000057171 uncertain significance not provided 2015-08-10 criteria provided, single submitter clinical testing The P14R missense substitution has not been published as a mutation or as a benign polymorphism to our knowledge. The P14R amino acid substitution is considered to be non-conservative as a neutral, polar Proline is being replaced by a basic, polar Arginine. In addition, the NHLBI ESP Exome Variant Server reports P14R was not observed in approximately 2000 control samples from individuals of European and African American backgrounds, indicating it is unlikely to be a common benign variant. However, this position is not highly conserved in this or related genes and is extremely variable in other species. Therefore, the interpretation of the pathogenicity of P14R is dependent upon the phenotype of the parent who harbors the variant. The variant is found in NOONAN panel(s).
Invitae RCV000654946 SCV000776854 uncertain significance Rasopathy 2017-08-24 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 14 of the BRAF protein (p.Pro14Arg). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and arginine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BRAF-related disease. ClinVar contains an entry for this variant (Variation ID: 40334). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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