Submissions for variant NM_002880.4(RAF1):c.1A>G (p.Met1Val)

dbSNP: rs2125453796

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002019360	SCV002284115	uncertain significance	RASopathy	2022-03-23	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Disruption of the initiator codon has been observed in individual(s) with dilated cardiomyopathy (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the RAF1 mRNA. The next in-frame methionine is located at codon 76.
Pediatric/Medical Genetics, Ministry of Health, Qatif Central Hospital	RCV004555630	SCV005044662	uncertain significance	LEOPARD syndrome 2; Noonan syndrome 5		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004738490	SCV005362125	uncertain significance	RAF1-related disorder	2024-04-12	no assertion criteria provided	clinical testing	The RAF1 c.1A>G variant is predicted to disrupt the translation initiation site (Start loss). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.