Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252827 | SCV002522761 | uncertain significance | See cases | 2021-01-28 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 |
Labcorp Genetics |
RCV005225578 | SCV005863272 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset | 2024-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 335 of the SQSTM1 protein (p.Asp335Glu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with Paget disease (PMID: 19067022). ClinVar contains an entry for this variant (Variation ID: 1690409). 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 SQSTM1 protein function with a negative 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. |