ClinVar Miner

Submissions for variant NM_003900.5(SQSTM1):c.662C>T (p.Thr221Met)

dbSNP: rs199663339
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798436 SCV000938053 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset 2023-09-04 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of SQSTM1-related conditions (PMID: 33601107). 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: 644501). This variant is present in population databases (rs199663339, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 221 of the SQSTM1 protein (p.Thr221Met).
GeneDx RCV001772056 SCV002003693 uncertain significance not provided 2021-04-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Previously reported as a variant of uncertain significance in an individual with Parkinsonism (Picillo et al., 2021); This variant is associated with the following publications: (PMID: 33601107, 25796131)
PreventionGenetics, part of Exact Sciences RCV004735808 SCV005346354 uncertain significance SQSTM1-related disorder 2024-04-11 no assertion criteria provided clinical testing The SQSTM1 c.662C>T variant is predicted to result in the amino acid substitution p.Thr221Met. This variant was reported in an individual with parkinsonism and cognitive-behavioral syndrome (Picillo et al. 2021. PubMed ID: 33601107). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.