ClinVar Miner

Submissions for variant NM_003900.5(SQSTM1):c.1139C>T (p.Ala380Val)

gnomAD frequency: 0.00001  dbSNP: rs1447276382
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002039963 SCV002110012 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset 2023-12-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 380 of the SQSTM1 protein (p.Ala380Val). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 1352802). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SQSTM1 protein function. 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.
CeGaT Center for Human Genetics Tuebingen RCV003334056 SCV004042245 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing SQSTM1: PS4:Supporting
PreventionGenetics, part of Exact Sciences RCV004529028 SCV004104630 uncertain significance SQSTM1-related disorder 2023-09-29 criteria provided, single submitter clinical testing The SQSTM1 c.1139C>T variant is predicted to result in the amino acid substitution p.Ala380Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-179260756-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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