Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004766992 | SCV005381114 | likely pathogenic | Growth hormone insensitivity syndrome | 2024-08-14 | criteria provided, single submitter | clinical testing | Variant summary: GHR c.184G>A (p.Glu62Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251356 control chromosomes (gnomAD). c.184G>A has been reported in the literature in an individuals affected with partial growth hormone insensitivity and short stature (Goddard_1995). These data do not allow any conclusion about variant significance. This publication reports experimental evidence evaluating an impact on protein function, finding that the variant resulted in severely impaired GH binding. The following publication has been ascertained in the context of this evaluation (PMID: 7565946). ClinVar contains an entry for this variant (Variation ID: 8636). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV005089214 | SCV005834469 | uncertain significance | not provided | 2024-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 62 of the GHR protein (p.Glu62Lys). This variant is present in population databases (rs121909361, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of autosomal dominant growth hormone insensitivity syndrome (PMID: 7565946). This variant is also known as Glu44Lys. ClinVar contains an entry for this variant (Variation ID: 8636). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GHR protein function with a negative predictive value of 80%. 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. |
| OMIM | RCV000009168 | SCV000029385 | pathogenic | Short stature due to partial GHR deficiency | 1995-10-26 | no assertion criteria provided | literature only |