Submissions for variant NM_002880.4(RAF1):c.1830A>G (p.Gln610=)

gnomAD frequency: 0.00088  dbSNP: rs141791080

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000149839	SCV000616479	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.1830A>G (p.Gln610=) variant in the RAF1 gene is 0.11% (88/66740) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037682	SCV000061344	likely benign	not specified	2015-04-09	criteria provided, single submitter	clinical testing	p.Gln610Gln in exon 17 of RAF1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.1% (88/66740) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs141791080).
Invitae	RCV000149839	SCV000287739	benign	RASopathy	2024-01-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528154	SCV000309259	benign	RAF1-related disorder	2021-08-06	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV000242861	SCV000319650	likely benign	Cardiovascular phenotype	2015-05-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000350733	SCV000440617	uncertain significance	Noonan syndrome 5	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000390530	SCV000440618	benign	LEOPARD syndrome 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Eurofins Ntd Llc (ga)	RCV000037682	SCV000861515	benign	not specified	2018-06-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756586	SCV000884441	benign	not provided	2018-05-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000756586	SCV001885546	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756586	SCV004146970	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	RAF1: BP4, BP7
Baylor Genetics	RCV000149839	SCV000196683	benign	RASopathy		no assertion criteria provided	clinical testing	Variant classified using ACMG guidelines