ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1207C>G (p.Pro403Ala) (rs749792302)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000591877 SCV000706414 likely benign not specified 2017-02-21 criteria provided, single submitter clinical testing
GeneDx RCV000681080 SCV000808534 uncertain significance not provided 2018-01-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the BRAF gene. The P403A variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The P403A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Nevertheless, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae RCV001345452 SCV001539571 uncertain significance Rasopathy 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 403 of the BRAF protein (p.Pro403Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs749792302, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 500454). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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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