Submissions for variant NM_001366385.1(CARD14):c.646G>A (p.Ala216Thr)

gnomAD frequency: 0.00005  dbSNP: rs574982768

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001979111	SCV002219742	uncertain significance	Pityriasis rubra pilaris; Psoriasis 2	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 216 of the CARD14 protein (p.Ala216Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with psoriasis (PMID: 24999592, 26203641, 30387497). ClinVar contains an entry for this variant (Variation ID: 1441466). 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%. Experimental studies have shown that this missense change affects CARD14 function (PMID: 26358359). 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	RCV002264433	SCV002543326	uncertain significance	Autoinflammatory syndrome	2017-03-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002264432	SCV002545982	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	CARD14: BP4