Submissions for variant NM_007373.4(SHOC2):c.1239G>T (p.Gln413His)

gnomAD frequency: 0.00006  dbSNP: rs200215822

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087569	SCV000261770	likely benign	RASopathy	2024-10-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000378748	SCV000360445	benign	Noonan syndrome-like disorder with loose anagen hair 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.
GeneDx	RCV000414482	SCV000490998	likely benign	not provided	2020-12-11	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar (ClinVar Variant ID# 220874; Landrum et al., 2016)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235129	SCV003933894	likely benign	not specified	2024-11-27	criteria provided, single submitter	clinical testing	Variant summary: SHOC2 c.1239G>T (p.Gln413His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 251394 control chromosomes. The observed variant frequency is approximately 6.046 fold of the estimated maximal expected allele frequency for a pathogenic variant in SHOC2 causing Noonan Syndrome With Loose Anagen Hair phenotype (2.5e-05). To our knowledge, no occurrence of c.1239G>T in individuals affected with Noonan Syndrome With Loose Anagen Hair and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 220874). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003967555	SCV004782174	likely benign	SHOC2-related disorder	2020-10-02	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).