Submissions for variant NM_001378743.1(CYLD):c.2273G>A (p.Arg758Gln)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV004770870	SCV005377123	uncertain significance	not provided	2023-11-19	criteria provided, single submitter	clinical testing	Has not been previously published as a pathogenic or benign germline variant to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27647909, 37389703, Deng2019[Abstract])
Labcorp Genetics (formerly Invitae), Labcorp	RCV004770870	SCV005796372	uncertain significance	not provided	2024-05-21	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 758 of the CYLD protein (p.Arg758Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CYLD-related conditions. 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 expected to disrupt CYLD protein function with a positive 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.