Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Lupski Lab, |
RCV000180777 | SCV000256755 | pathogenic | Autoimmune interstitial lung disease-arthritis syndrome | 2015-04-20 | criteria provided, single submitter | research | Segregates with the phenotype in an affected family. The family showed incomplete penetrance, with unaffected carriers over three generations. |
Invitae | RCV000180777 | SCV002174229 | uncertain significance | Autoimmune interstitial lung disease-arthritis syndrome | 2021-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 243 of the COPA protein (p.Asp243Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of autoimmune interstitial lung, joint, and kidney disease (PMID: 25894502). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 199255). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COPA protein function. Experimental studies have shown that this missense change affects COPA function (PMID: 25894502). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV000180777 | SCV000233265 | pathogenic | Autoimmune interstitial lung disease-arthritis syndrome | 2015-06-01 | no assertion criteria provided | literature only |