Submissions for variant NM_002880.4(RAF1):c.1850A>T (p.Asn617Ile)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002413000	SCV002717125	uncertain significance	Cardiovascular phenotype	2022-06-27	criteria provided, single submitter	clinical testing	The p.N617I variant (also known as c.1850A>T), located in coding exon 16 of the RAF1 gene, results from an A to T substitution at nucleotide position 1850. The asparagine at codon 617 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV002466757	SCV002762230	likely pathogenic	not provided	2022-06-10	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24077912, 29493581)
Illumina Laboratory Services, Illumina	RCV003985107	SCV004801571	uncertain significance	Noonan syndrome 5	2019-07-26	criteria provided, single submitter	clinical testing	The RAF1 c.1850A>T p.(Asn617Ile) missense variant, to our knowledge, has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 4.0.0 of the Genome Aggregation Database. Based on the limited evidence, the c.1850A>T p.(Asn617Ile) variant is classified as a variant of uncertain significance for Noonan syndrome.