Submissions for variant NM_001366385.1(CARD14):c.1012A>G (p.Met338Val)

gnomAD frequency: 0.00008  dbSNP: rs200132496

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001998189	SCV002257516	uncertain significance	Pityriasis rubra pilaris; Psoriasis 2	2024-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 338 of the CARD14 protein (p.Met338Val). This variant is present in population databases (rs200132496, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with psoriasis vulgaris (PMID: 26358359). ClinVar contains an entry for this variant (Variation ID: 1476693). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264440	SCV002543143	uncertain significance	Autoinflammatory syndrome	2021-10-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003948855	SCV004765644	likely benign	CARD14-related disorder	2022-06-28	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).