Submissions for variant NM_005633.4(SOS1):c.73C>T (p.Pro25Ser)

gnomAD frequency: 0.00082  dbSNP: rs139592595

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000521504	SCV000616436	benign	RASopathy	2017-04-03	reviewed by expert panel	curation	The filtering allele frequency of the c.73C>T (p.Pro25Ser) variant in the SOS1 gene is 0.23% for African chromosomes by the Exome Aggregation Consortium (21/6116 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154848	SCV000204530	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Pro25Ser in Exon 01 of SOS1: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (12/3732) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs139592595).
GeneDx	RCV001711220	SCV000209065	benign	not provided	2019-01-11	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000154848	SCV000224487	likely benign	not specified	2015-06-18	criteria provided, single submitter	clinical testing
Invitae	RCV000521504	SCV000659152	likely benign	RASopathy	2024-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381283	SCV002673540	benign	Cardiovascular phenotype	2019-03-26	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	RCV002482943	SCV002796697	likely benign	Fibromatosis, gingival, 1; Noonan syndrome 4	2021-12-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001711220	SCV004145981	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	SOS1: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003934876	SCV004754123	likely benign	SOS1-related disorder	2019-10-07	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).