ClinVar Miner

Submissions for variant NM_003900.5(SQSTM1):c.1178G>A (p.Arg393Gln)

gnomAD frequency: 0.00004  dbSNP: rs200551825
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528145 SCV000655591 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Paget disease of bone 2, early-onset 2024-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 393 of the SQSTM1 protein (p.Arg393Gln). This variant is present in population databases (rs200551825, gnomAD 0.02%). 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: 475395). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
PreventionGenetics, part of Exact Sciences RCV004538077 SCV004727183 uncertain significance SQSTM1-related disorder 2023-10-30 no assertion criteria provided clinical testing The SQSTM1 c.1178G>A variant is predicted to result in the amino acid substitution p.Arg393Gln. This variant was reported in an individual with amyotrophic lateral sclerosis (Tripolszki et al 2019. PubMed ID: 31475037). This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-179263448-G-A). 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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