Submissions for variant NM_025132.4(WDR19):c.553C>G (p.Gln185Glu)

dbSNP: rs769602871

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001882779	SCV002257677	uncertain significance	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 185 of the WDR19 protein (p.Gln185Glu). This variant is present in population databases (rs769602871, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. ClinVar contains an entry for this variant (Variation ID: 1285210). 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 WDR19 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001702023	SCV004564258	uncertain significance	not provided	2022-12-22	criteria provided, single submitter	clinical testing	The WDR19 c.553C>G; p.Gln185Glu variant (rs769602871), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1285210). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamine at codon 185 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.059). Due to limited information, the clinical significance of this variant is uncertain at this time.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702023	SCV001932892	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702023	SCV001973361	likely benign	not provided		no assertion criteria provided	clinical testing