ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.316G>A (p.Gly106Arg) (rs749247588)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000610566 SCV000712243 uncertain significance not specified 2016-10-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Gly106Arg var iant in BRAF has been previously identified in 1 individual with clinical featur es of Noonan syndrome, but was also identified in an unaffected parent (LMM data ). It has been identified 1/66687 European and 1/16503 South Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs749247588). Computational prediction tools and conservation analysis suggest t hat the p.Gly106Arg variant may impact the protein, though this information is n ot predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Gly106Arg variant is uncertain, these data suggest that i t is more likely to be benign.
Invitae RCV000794440 SCV000933848 uncertain significance Rasopathy 2019-01-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 106 of the BRAF protein (p.Gly106Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs749247588, ExAC 0.006%). This variant has been reported in an individual affected with neurofibromatosis type-1, however this individual also carried a pathogenic NF1 variant  (PMID: 30290804)  ClinVar contains an entry for this variant (Variation ID: 505121). 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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