Submissions for variant NM_004333.6(BRAF):c.1397G>A (p.Gly466Glu)

dbSNP: rs121913351

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861476	SCV002171637	uncertain significance	RASopathy	2021-02-14	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with cardio-facio-cutaneous syndrome (PMID: 21062266). ClinVar contains an entry for this variant (Variation ID: 376073). 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. This variant disrupts the p.Gly466 amino acid residue in BRAF. Other variant(s) that disrupt this residue have been observed in individuals with BRAF-related conditions (PMID: 31336229), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt BRAF protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 466 of the BRAF protein (p.Gly466Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV003128083	SCV003804259	likely pathogenic	Noonan syndrome 7	2023-01-23	criteria provided, single submitter	clinical testing