Submissions for variant NM_001366385.1(CARD14):c.956G>A (p.Arg319Gln)

gnomAD frequency: 0.00006  dbSNP: rs138991161

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001222308	SCV001394402	uncertain significance	Pityriasis rubra pilaris; Psoriasis 2	2023-12-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 319 of the CARD14 protein (p.Arg319Gln). This variant is present in population databases (rs138991161, gnomAD 0.01%). This missense change has been observed in individual(s) with familial Mediterranean fever, however the individual also carried variants in the MEFV gene (PMID: 32199921). ClinVar contains an entry for this variant (Variation ID: 950569). 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 CARD14 protein function with a negative predictive value of 80%. 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.