Submissions for variant NM_006939.4(SOS2):c.549G>C (p.Leu183Phe)

gnomAD frequency: 0.00083  dbSNP: rs137961578

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001079947	SCV000656032	likely benign	Noonan syndrome 9	2024-01-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586255	SCV000698746	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.549G>C (p.Leu183Phe) variant causes a missense change involving the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). The variant of interest has been found in a large, broad control population, ExAC in 116/119774 control chromosomes at a frequency of 0.0009685, which is approximately 387 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000608191	SCV000714911	benign	not specified	2017-07-03	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813502	SCV002060680	benign	Noonan syndrome and Noonan-related syndrome	2021-02-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002350385	SCV002651029	benign	Cardiovascular phenotype	2019-09-17	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.
Genome-Nilou Lab	RCV001079947	SCV002763129	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001079947	SCV003799223	likely benign	Noonan syndrome 9	2022-05-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586255	SCV004033295	benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	SOS2: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003935541	SCV004749748	likely benign	SOS2-related disorder	2020-08-12	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).
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001261119	SCV001438526	likely benign	Noonan syndrome		no assertion criteria provided	clinical testing