Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001999210 | SCV002287307 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset | 2024-05-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 139 of the SQSTM1 protein (p.Arg139Cys). This variant is present in population databases (rs750256905, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SQSTM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498430). 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 SQSTM1 protein function with a positive 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. |
| Gene |
RCV003159227 | SCV003853127 | uncertain significance | not provided | 2022-09-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |