ClinVar Miner

Submissions for variant NM_016953.4(PDE11A):c.171del (p.Thr58fs) (rs529789124)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000190613 SCV000245648 uncertain significance Pigmented nodular adrenocortical disease, primary, 2 2014-10-21 criteria provided, single submitter clinical testing The p.Thr58ProfsX41 variant in PDE11A has been reported in 1 individual with adrenocortical hyperplasia and Cushing syndrome, and segregated with disease in 1 parent with hypertension, obesity, and bilaterally enlarged adrenal glands (Horvath 2006). This variant has also been reported in 1 individual with acromegaly (Peverelli 2009) and in 3 individuals with Carney complex who also carried PRKAR1A variants, and was considered to be a possible modifier of disease in these individuals (Libe 2011). This variant has been identified in 5/8254 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). The p.Thr58ProfsX41 variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 58 and leads to a premature termination codon 41 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Several loss-of-function PDE11A variants have been described in individuals with Cushing syndrome and with adrenal hyperplasia with established loss-of-heterozygosity in somatic tissue (Horvath 2006, Carney 2010, Libe 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Thr58ProfsX41 variant is uncertain.
GeneDx RCV000485692 SCV000565363 benign not specified 2016-07-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000903265 SCV001047723 benign not provided 2019-02-14 criteria provided, single submitter clinical testing
OMIM RCV000190613 SCV000025787 uncertain significance Pigmented nodular adrenocortical disease, primary, 2 2006-07-01 no assertion criteria provided literature only

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