Submissions for variant NM_002880.4(RAF1):c.1914G>A (p.Thr638=)

gnomAD frequency: 0.00001  dbSNP: rs144876026

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000519653	SCV000616478	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.1914G>A (p.Thr638=) variant in the RAF1 gene is 0.926% (174/16512) of South Asian 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	RCV000037684	SCV000061346	benign	not specified	2015-08-10	criteria provided, single submitter	clinical testing	p.Thr638Thr 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 1% (174/16512) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org/; dbSNP rs144876026).
PreventionGenetics, part of Exact Sciences	RCV000037684	SCV000309260	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242024	SCV000319656	benign	Cardiovascular phenotype	2015-05-21	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000402345	SCV000440615	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.
Illumina Laboratory Services, Illumina	RCV000279428	SCV000440616	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000519653	SCV000659055	benign	RASopathy	2024-01-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037684	SCV001360610	benign	not specified	2019-08-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001705628	SCV001915674	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813274	SCV002060608	benign	Noonan syndrome and Noonan-related syndrome	2021-04-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001705628	SCV004146969	benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	RAF1: BP4, BP7, BS1, BS2