Submissions for variant NM_005633.4(SOS1):c.1074+5G>C

gnomAD frequency: 0.00655  dbSNP: rs145155424

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000128195	SCV000616521	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.1074+5G>C variant in the SOS1 gene is 1.551% (837/50942) 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	RCV000038508	SCV000062186	benign	not specified	2011-03-25	criteria provided, single submitter	clinical testing	1074+5G>C in intron 8 of SOS1: This variant has not been previously reported in the literature. However, this variant has been identified in 12/1154 (1%) of ind ividual's tested by our laboratory, two of whom have a pathogenic variant in PTP N11. In addition, this variant is located in the 5' splice region but does not a ffect the highly conserved +1 and +2 positions. However, positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions s ometimes affect splicing. This type of variant has not been previously reported as pathogenic in SOS1. Therefore, this variant is likely to be benign.
Eurofins Ntd Llc (ga)	RCV000038508	SCV000113236	benign	not specified	2013-05-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000038508	SCV000171787	benign	not specified	2011-12-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000128195	SCV000261490	benign	RASopathy	2024-02-01	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224268	SCV000280994	likely benign	not provided	2016-04-21	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences	RCV000038508	SCV000311181	benign	not specified	2010-07-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094608	SCV000430439	likely benign	Noonan syndrome 4	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000296571	SCV000430440	benign	Fibromatosis, gingival, 1	2018-01-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000224268	SCV001156971	benign	not provided	2023-10-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813353	SCV002060629	benign	Noonan syndrome and Noonan-related syndrome	2021-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224268	SCV002544025	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SOS1: BP4, BS1, BS2
Ambry Genetics	RCV002415476	SCV002721680	benign	Cardiovascular phenotype	2016-05-13	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.
Fulgent Genetics, Fulgent Genetics	RCV002477103	SCV002794862	benign	Fibromatosis, gingival, 1; Noonan syndrome 4	2021-10-08	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000038508	SCV000207692	benign	not specified	2015-01-15	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000224268	SCV001800312	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000038508	SCV001808822	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038508	SCV001921109	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000224268	SCV001929404	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000224268	SCV001960029	likely benign	not provided		no assertion criteria provided	clinical testing