Submissions for variant NM_006005.3(WFS1):c.47C>T (p.Pro16Leu)

dbSNP: rs34653805

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001795764	SCV002172156	uncertain significance	not provided	2023-11-28	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 16 of the WFS1 protein (p.Pro16Leu). This variant is present in population databases (rs34653805, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1328332). 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 WFS1 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795764	SCV002036050	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001795764	SCV002038031	likely benign	not provided		no assertion criteria provided	clinical testing