Submissions for variant NM_004333.6(BRAF):c.1411G>A (p.Val471Ile)

dbSNP: rs121913376

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000033309	SCV000057214	likely pathogenic	not provided	2012-08-30	criteria provided, single submitter	clinical testing	The V471I missense change has not been published as a germline mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Server reports that V471I was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. The V471I amino acid substitution is conservative as both Valine and Isoleucine are neutral and non-polar residues. However, the V471 position is highly conserved across species and in related proteins. A different mutation (V471F) at this same position and many other missense mutations of nearby codons (S467A, F468S, G469E, L485F, L485S) have been published in association with cardio-facio-cutaneous syndrome (CFC) (Abe et al., 2012; Rodriguez-Viciana et al., 2006; Niihori et al., 2006; Rodriguez-Viciana et al., 2008; Aoki et al., 2008). Therefore, V471I is a strong candidate for a disease-causing mutation, although the possibility that it is a benign polymorphism cannot be excluded. The variant is found in NOONAN panel(s).