ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.293G>A (p.Arg98Gln)

gnomAD frequency: 0.00001  dbSNP: rs1478204355
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796897 SCV000936431 uncertain significance Tuberous sclerosis 2 2023-12-24 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 98 of the TSC2 protein (p.Arg98Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 643234). 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 TSC2 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects TSC2 function (PMID: 36229297). 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.
GeneDx RCV001840733 SCV002099633 uncertain significance not provided 2021-08-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115)
Ambry Genetics RCV002440646 SCV002750225 likely benign Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002487669 SCV002781108 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2022-03-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV003461091 SCV004204532 uncertain significance Isolated focal cortical dysplasia type II 2023-10-15 criteria provided, single submitter clinical testing

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