Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002948877 | SCV003276796 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset | 2023-09-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SQSTM1-related conditions. 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 SQSTM1 protein function. ClinVar contains an entry for this variant (Variation ID: 2066043). This variant is present in population databases (rs763972646, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 212 of the SQSTM1 protein (p.Arg212His). |
| Ambry Genetics | RCV002948876 | SCV003716318 | uncertain significance | Inborn genetic diseases | 2021-10-02 | criteria provided, single submitter | clinical testing | The c.635G>A (p.R212H) alteration is located in exon 4 (coding exon 4) of the SQSTM1 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |