ClinVar Miner

Submissions for variant NM_004371.4(COPA):c.698G>A (p.Arg233His) (rs794727993)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000180776 SCV000256756 pathogenic Autoimmune interstitial lung, joint, and kidney disease 2015-04-20 criteria provided, single submitter research Segregates with the phenotype in two affected families. One family showed incomplete penetrance, with one unaffected carrier over four generations.
Invitae RCV000180776 SCV000774975 pathogenic Autoimmune interstitial lung, joint, and kidney disease 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 233 of the COPA protein (p.Arg233His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autoimmune-mediated lung disease and arthritis in two families (PMID: 25894502). ClinVar contains an entry for this variant (Variation ID: 199254). Experimental studies in patient lung biopsies and transfected cell lines have shown that this missense change results in increased levels of molecular chaperone binding immunoglobulin protein (BiP), which is an indicator of ER stress (PMID: 25894502). For these reasons, this variant has been classified as Pathogenic.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000180776 SCV000930528 pathogenic Autoimmune interstitial lung, joint, and kidney disease 2019-08-01 criteria provided, single submitter clinical testing identified in different affected members of same family
OMIM RCV000180776 SCV000233264 pathogenic Autoimmune interstitial lung, joint, and kidney disease 2015-06-01 no assertion criteria provided literature only

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