Submissions for variant NM_005633.4(SOS1):c.3737A>G (p.Asn1246Ser)

gnomAD frequency: 0.00004  dbSNP: rs374110460

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001577043	SCV001804360	uncertain significance	not provided	2019-03-28	criteria provided, single submitter	clinical testing	The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014; Hart et al., 2002); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002343752	SCV002621205	uncertain significance	Cardiovascular phenotype	2021-06-01	criteria provided, single submitter	clinical testing	The p.N1246S variant (also known as c.3737A>G), located in coding exon 23 of the SOS1 gene, results from an A to G substitution at nucleotide position 3737. The asparagine at codon 1246 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV002468277	SCV002763542	uncertain significance	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002468276	SCV002763543	uncertain significance	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002570808	SCV003514178	benign	RASopathy	2023-04-28	criteria provided, single submitter	clinical testing