Submissions for variant NM_002880.4(RAF1):c.1895_1918del (p.Glu632_Thr640delinsAla)

gnomAD frequency: 0.00001  dbSNP: rs2058255431

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193741	SCV001362805	uncertain significance	not specified	2019-10-22	criteria provided, single submitter	clinical testing	Variant summary: RAF1 c.1895_1918del24 (p.Glu632_Thr640delinsAla) results in an in-frame deletion-insertion that is predicted to delete 9 amino acids and insert one amino acid. The variant was absent in 251278 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1895_1918del24 in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005094030	SCV005823044	uncertain significance	RASopathy	2024-02-13	criteria provided, single submitter	clinical testing	This variant, c.1895_1918del, is a complex sequence change that results in the deletion of 9 and insertion of 1 amino acid(s) in the RAF1 protein (p.Glu632_Thr640delinsAla). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 928992). 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.