Submissions for variant NM_007373.4(SHOC2):c.363G>A (p.Glu121=)

gnomAD frequency: 0.00007  dbSNP: rs115713408

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000520874	SCV000616493	likely benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.363G>A (p.Glu121=) variant in the SHOC2 gene is 0.0384% (8/10350) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000520874	SCV001003146	likely benign	RASopathy	2023-10-20	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813493	SCV002060625	likely benign	Noonan syndrome and Noonan-related syndrome	2020-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002455998	SCV002613742	likely benign	Cardiovascular phenotype	2020-06-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
PreventionGenetics, part of Exact Sciences	RCV004752929	SCV005349791	likely benign	SHOC2-related disorder	2020-08-25	no assertion criteria provided	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).