Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001851006 | SCV000619661 | uncertain significance | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | Reported as a variant of uncertain significance in a patient referred for whole exome sequencing who was also compound heterozygous for another variant of uncertain significance in WFS1 (PMID: 27959697); patient clinical information not provided; 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: 26435059, 31264968, 27959697) |
| Genomic Research Center, |
RCV000714795 | SCV000845528 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 6 | 2018-08-07 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000765777 | SCV000897166 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001851006 | SCV002178566 | uncertain significance | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 360 of the WFS1 protein (p.Cys360Tyr). This variant is present in population databases (rs147157374, gnomAD 0.02%). This missense change has been observed in individual(s) with multiple congenital anomalies or with type 1 diabetes (PMID: 27959697, 31264968). ClinVar contains an entry for this variant (Variation ID: 374398). 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 WFS1 protein function with a positive 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. |
| Mayo Clinic Laboratories, |
RCV001851006 | SCV004226969 | uncertain significance | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | PP3, PM2_supporting |
| Baylor Genetics | RCV000414884 | SCV000328754 | uncertain significance | Wolfram syndrome 1 | 2014-09-24 | no assertion criteria provided | clinical testing | Our laboratory reported dual molecular diagnoses in ACTG1 (NM_001199954.1, c.118C>T) and WFS1 (NM_001145853.1, c.2191A>G and c.1079G>A in trans) in one individual with reported features of delayed motor milestones, delayed speech, mild intellectual disability, congenital bilateral sensorineural hearing loss, dysmorphic features and eye anomalies (strabismus, possible cortical visual impairment). Brain MRI showed dysplastic corpus callosum and possible intracranial lipoma. Additionally, this variant was seen once in our laboratory in trans with another missense variant (c.2452C>T) in a 22-year-old male with muscle weakness, obesity and type II diabetes, hypertension, fatigue and fibromyalgia, primary hypothyroidism, thymic hyperplasia, short stature, and nonalcoholic steatohepatitis |