Submissions for variant NM_000163.5(GHR):c.535C>T (p.Arg179Cys) (rs121909362)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000723957	SCV000231487	uncertain significance	not provided	2018-07-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000255291	SCV000321723	uncertain significance	not specified	2017-10-05	criteria provided, single submitter	clinical testing	The R179C variant in the GHR gene has been reported previously in the homozygous state in an individual with Laron syndrome (Amselem et al., 1993) and in the compound heterozygous state along with another missense GHR variant in a child with idiopathic short stature (Goddard et al., 1995). Note that in both reports this variant was reported as R161C due to differences in nomenclature. The R179C variant has also been identified in the heterozygous state in an adult with mild short stature (Meyer et al., 2007). The R179C variant is observed in 737/126,246 alleles (0.58%) from individuals of non-Finnish European background and 97/30,778 alleles (0.32%) from individuals of South Asian ancestry in large population cohorts, including a combined total of 4 homozygous control individuals (Lek et al., 2016). The R179C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We therefore interpret R179C as a variant of uncertain significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000660368	SCV000782439	uncertain significance	Laron-type isolated somatotropin defect; Short stature, idiopathic, autosomal	2016-05-09	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000764609	SCV000895708	uncertain significance	Laron-type isolated somatotropin defect; Short stature, idiopathic, autosomal; Familial hypercholesterolemia 1; Short stature due to growth hormone secretagogue receptor deficiency	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000723957	SCV001012287	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000723957	SCV001154400	uncertain significance	not provided	2017-06-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001156022	SCV001317495	likely benign	Laron-type isolated somatotropin defect	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
OMIM	RCV000009169	SCV000029386	pathogenic	Short stature, idiopathic, autosomal	1995-10-26	no assertion criteria provided	literature only