Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001851615 | SCV006088101 | likely pathogenic | not provided | 2024-12-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate very low activity when stimulated with high doses of ACTH (PMID: 12213892); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18840636, 12213892, 26523528, 32952553, 10971458, 15673970, 38430736) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000003421 | SCV005727071 | pathogenic | Glucocorticoid deficiency 1 | 2024-11-06 | criteria provided, single submitter | clinical testing | Variant summary: MC2R c.409C>T (p.Arg137Trp) results in a non-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 6e-05 in 251244 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MC2R causing Glucocorticoid Deficiency, Due To ACTH Unresponsiveness, allowing no conclusion about variant significance. c.409C>T has been reported in the literature in individuals affected with Glucocorticoid Deficiency (example: Ishii_2000, Fluck_2002, Guran_2015). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence that variant reduced normal activity (Fluck_2002). The following publications have been ascertained in the context of this evaluation (PMID: 12213892, 26523528, 10971458). ClinVar contains an entry for this variant (Variation ID: 3265). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001851615 | SCV002146499 | pathogenic | not provided | 2021-09-02 | criteria provided, single submitter | clinical testing | |
| Clinical Molecular Genetics Laboratory, |
RCV000584506 | SCV000692309 | pathogenic | Glucocorticoid Deficiency | 2008-04-16 | no assertion criteria provided | clinical testing | |
| OMIM | RCV000003421 | SCV000023579 | pathogenic | Glucocorticoid deficiency 1 | 2002-09-01 | no assertion criteria provided | literature only |