Submissions for variant NM_000163.5(GHR):c.718T>C (p.Tyr240His)

gnomAD frequency: 0.00024  dbSNP: rs143814221

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179726	SCV000232020	uncertain significance	not provided	2014-12-18	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626627	SCV000747328	pathogenic	Seizure; Short stature; Specific learning disability; Genu varum; Relative macrocephaly; Mesomelic/rhizomelic limb shortening; Disproportionate short-limb short stature	2017-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000581226	SCV001317497	uncertain significance	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198886	SCV001369881	uncertain significance	Short stature due to partial GHR deficiency	2020-04-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Invitae	RCV000179726	SCV002189621	uncertain significance	not provided	2022-10-12	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 240 of the GHR protein (p.Tyr240His). This variant is present in population databases (rs143814221, gnomAD 0.05%). This missense change has been observed in individual(s) with growth hormone insensitivity (PMID: 10984309). This variant is also known as p.Tyr222His. ClinVar contains an entry for this variant (Variation ID: 198398). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GHR protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
New York Genome Center	RCV003448279	SCV004176170	uncertain significance	Laron-type isolated somatotropin defect; Short stature due to partial GHR deficiency	2023-09-01	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000581226	SCV000692135	pathogenic	Laron-type isolated somatotropin defect	2017-05-04	no assertion criteria provided	clinical testing