Submissions for variant NM_005633.4(SOS1):c.570C>T (p.Asp190=)

gnomAD frequency: 0.00233  dbSNP: rs55980502

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000467119	SCV000616523	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.570C>T (p.Asp190=) variant in the SOS1 gene is 0.314% (234/66628) 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	RCV000038565	SCV000062243	benign	not specified	2011-06-09	criteria provided, single submitter	clinical testing	Asp190Asp in exon 5 of SOS1: This variant (rs55980502) is not expected to have c linical signficance because it does not alter an amino acid residue and is not l ocated near a splice junction. In addition, this variant has been identified in the unaffected parent of one proband and two probands that have pathogenic varia nts in PTPN11 tested by our laboratory.
Eurofins Ntd Llc (ga)	RCV000038565	SCV000339643	benign	not specified	2016-02-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000323571	SCV000430449	likely benign	Noonan syndrome 4	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.
Illumina Laboratory Services, Illumina	RCV000355188	SCV000430450	benign	Fibromatosis, gingival, 1	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.
Invitae	RCV000467119	SCV000563107	benign	RASopathy	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756675	SCV000884558	benign	not provided	2017-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000756675	SCV001868773	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813281	SCV002060658	benign	Noonan syndrome and Noonan-related syndrome	2020-09-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345264	SCV002650596	benign	Cardiovascular phenotype	2019-01-25	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	RCV002504858	SCV002798468	likely benign	Fibromatosis, gingival, 1; Noonan syndrome 4	2022-02-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756675	SCV004145980	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	SOS1: BP4, BS1
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000756675	SCV001808290	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038565	SCV001919573	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756675	SCV001974226	likely benign	not provided		no assertion criteria provided	clinical testing