Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000817174 | SCV000957720 | likely pathogenic | Pityriasis rubra pilaris; Psoriasis 2 | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 119 of the CARD14 protein (p.Met119Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of pityriasis rubra pilaris (PMID: 29477734, 34004138, 34448248). ClinVar contains an entry for this variant (Variation ID: 660052). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CARD14 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects CARD14 function (PMID: 34004138). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Yale Center for Mendelian Genomics, |
RCV000845188 | SCV000987124 | pathogenic | Papulosquamous eruptions | 2018-03-01 | no assertion criteria provided | literature only |