ClinVar Miner

Submissions for variant NM_000529.2(MC2R):c.221G>T (p.Ser74Ile) (rs104894658)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000583288 SCV000692308 pathogenic Glucocorticoid Deficiency 2009-01-23 no assertion criteria provided clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000003414 SCV000914807 pathogenic ACTH resistance 2018-12-19 criteria provided, single submitter clinical testing Across a selection of the available literature, the MCR2 c.221G>T (p.Ser74Ile) variant has been identified in upwards of 45 individuals with glucocorticoid deficiency in either a homozygous or compound heterozygous state (Clark and Weber 1994; Lin et al. 2007; Chan et al. 2009; Chung et al. 2010; Matthew et al. 2011; Tsai et al, 2016). The p.Ser74Ile variant is reported at a frequency of 0.00035 in the European American population of the Exome Sequencing Project. Functional assays performed by Fluck et al. (2002) and Elias et al. (1999) demonstrated that the p.Ser74Ile variant elicited virtually no measurable enzymatic activity and was associated with an impaired maximal cAMP response when compared to wild type. Based on the collective evidence, the p.Ser74Ile variant is classified as pathogenic for glucocorticoid deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000003414 SCV000023572 pathogenic ACTH resistance 1993-02-20 no assertion criteria provided literature only

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