Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658092 | SCV000779863 | uncertain significance | not provided | 2018-05-22 | criteria provided, single submitter | clinical testing | The L573V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 6/126650 (0.0047%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). L573V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV000658092 | SCV002266214 | uncertain significance | not provided | 2023-06-29 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 546243). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs749172015, gnomAD 0.005%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 573 of the WFS1 protein (p.Leu573Val). |
| Fulgent Genetics, |
RCV002493069 | SCV002812331 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV003126895 | SCV003801428 | uncertain significance | Wolfram syndrome 1 | criteria provided, single submitter | research | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs749172015 in Wolfram's syndrome yet. |