ClinVar Miner

Submissions for variant NM_212472.2(PRKAR1A):c.682C>T (p.Arg228Ter) (rs281864784)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627207 SCV000748194 pathogenic not provided 2018-02-07 criteria provided, single submitter clinical testing The R228X nonsense pathogenic variant in the PRKAR1A gene has been reported previously in association with Carney Complex (Kirschner et al., 2000; Horvath et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000034293 SCV001231427 pathogenic Carney complex, type 1 2019-11-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg228*) in the PRKAR1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Carney complex (PMID: 11115848). This variant is also known as 769C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 41391). Loss-of-function variants in PRKAR1A are known to be pathogenic (PMID: 11115848, 19293268). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269128 SCV001448379 pathogenic Carney complex 2020-11-03 criteria provided, single submitter clinical testing Variant summary: PRKAR1A c.682C>T (p.Arg228X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251178 control chromosomes (gnomAD). c.682C>T has been reported in the literature in individuals affected with Carney Complex (Kirschner_2000, Courcoutsakis_2009, Libe_2010, Sikorska_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneReviews RCV000034293 SCV000058239 pathologic Carney complex, type 1 2012-09-20 no assertion criteria provided curation Converted during submission to Pathogenic.

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