ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1502A>T (p.Glu501Val) (rs180177039)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033318 SCV000057223 pathogenic not provided 2013-05-20 criteria provided, single submitter clinical testing p.Glu501Val (GAA>GTA): c.1502 A>T in exon 12 of the BRAF gene (NM_004333.4). The E501V missense mutation in the BRAF gene has been reported previously in association with CFC syndrome (Nava et al., 2007). The E501 codon appears to be a hot spot for gain-of-function mutations, as other amino acid substitutions altering this codon, E501G and E501K, have also been reported in patients with CFC syndrome (Niihori et al., 2006). The variant is found in NOONAN panel(s).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037924 SCV000061588 likely pathogenic Cardio-facio-cutaneous syndrome 2014-09-24 criteria provided, single submitter clinical testing The Glu501Val variant in BRAF has been reported in three individuals with clinic al features of Cardio-facio-cutaneous syndrome (Yoon 2007, Nava 2007, LMM unpubl ished data). It was also absent from large population studies. Different disease -causing amino acid changes (Glu501Lys, Glu501Gly) at this location have been id entified in >10 affected individuals and both of these variants were reported to have occurred de novo in two individuals (Razzaque 2007,Narumi 2007, Niihori 20 06, Rodriguez-Viciana 2006,Rodriguez-Viciana 2008, LMM unpublished data) suggest ing that changes at this position are not tolerated. Additionally, computational prediction tools and evolutionary conservation analysis suggest that the Glu501 Val variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, the Glu501Val variant is likely pa thogenic, though additional studies are required to fully establish its clinical significance.

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