Table 1.

Molecular Genetic Testing Used in Cardiofaciocutaneous (CFC) Syndrome

Gene 1, 2Proportion of CFC Syndrome Attributed to Pathogenic Variants in Gene 3Proportion of Probands with a Pathogenic Variant 4 Detectable by Method
Sequence analysis 5Gene-targeted deletion/duplication analysis 6
BRAF ~75%~100% 7Single deletion reported 8
KRAS <2%~100% 7Unknown 9
MAP2K1 ~25%~100% 7Unknown 9
MAP2K2 ~100% 7Several deletions have been reported, 10 but may not cause CFC syndrome. 11
Unknown 12NA

NA = not applicable


Genes are listed in alphabetic order.


See Molecular Genetics for information on variants detected in these genes.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]


A single report of a BRAF deletion associated with a CFC-like phenotype [Yu & Graf 2011] that was not supported by functional data


No data on detection rate of gene-targeted deletion/duplication analysis are available.


Nowaczyk et al [2014] reported several individuals with a MAP2K2 deletion associated with a CFC-like phenotype. This was supported by functional data of MAPK pathway dysregulation.


Lissewski et al [2015] disputed that gene deletions or duplications cause RASopathies.


Popov et al [2019] reported several individuals with features of CFC syndrome who had a heterozygous variant in YWHAZ.

From: Cardiofaciocutaneous Syndrome

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