Submissions for variant NM_003361.4(UMOD):c.1406C>A (p.Thr469Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV005019790	SCV005638463	uncertain significance	Familial juvenile hyperuricemic nephropathy type 1	2024-05-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005061874	SCV005694610	uncertain significance	not provided	2024-03-02	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 469 of the UMOD protein (p.Thr469Lys). This variant is present in population databases (rs143583842, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with UMOD-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 not expected to disrupt UMOD protein function with a negative predictive value of 95%. 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.