ClinVar Miner

Submissions for variant NM_002734.4(PRKAR1A):c.220C>T (p.Arg74Cys) (rs137853303)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148738 SCV000190474 uncertain significance Carney complex 2014-06-01 no assertion criteria provided research
Invitae RCV000013510 SCV000950751 uncertain significance Carney complex, type 1 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 74 of the PRKAR1A protein (p.Arg74Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Carney complex in a family (PMID: 15371594). ClinVar contains an entry for this variant (Variation ID: 12674). Experimental studies have reported conflicting results for this missense change. One study indicates that this variant does not affect R1-alpha protein levels and PKA activity (PMID: 15371594) and another has shown that it results in an increase of PKA activity and decrease binding to cAMP (PMID: 18241045). The clinical significance of these findings is uncertain. 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 RCV000013510 SCV000033757 pathogenic Carney complex, type 1 2008-05-01 no assertion criteria provided literature only

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