Submissions for variant NM_006005.3(WFS1):c.709G>A (p.Glu237Lys)

gnomAD frequency: 0.00001  dbSNP: rs763480468

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001700803	SCV002005004	uncertain significance	not provided	2019-08-12	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in a patient with type 2 diabetes mellitus in published literature (Kawamoto et al., 2004); This variant is associated with the following publications: (PMID: 15234338)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001700803	SCV004502417	uncertain significance	not provided	2024-11-30	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 237 of the WFS1 protein (p.Glu237Lys). This variant is present in population databases (rs763480468, gnomAD 0.003%). This missense change has been observed in individual(s) with WFS1-related conditions (PMID: 15234338). ClinVar contains an entry for this variant (Variation ID: 1284264). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WFS1 protein function. 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.
Fulgent Genetics, Fulgent Genetics	RCV005038280	SCV005664697	uncertain significance	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2024-02-28	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700803	SCV001925275	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700803	SCV001968345	uncertain significance	not provided		no assertion criteria provided	clinical testing