ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3095G>C (p.Arg1032Pro)

dbSNP: rs45491698
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000201071 SCV000255889 likely pathogenic Tuberous sclerosis 2 2015-07-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000201071 SCV000644403 pathogenic Tuberous sclerosis 2 2024-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1032 of the TSC2 protein (p.Arg1032Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with tuberous sclerosis complex (TSC) (PMID: 21520333). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 49241). 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 expected to disrupt TSC2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TSC2 function (PMID: 21309039). For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University RCV000201071 SCV001423569 likely pathogenic Tuberous sclerosis 2 2020-07-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000201071 SCV002040965 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV005255560 SCV005908387 pathogenic not provided 2024-10-14 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect and indicate that this variant disrupts the TSC1 TSC2 complex and is pathogenic (PMID: 21309039); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31454656, 15798777, 31855466, 32555378, 21309039, 36232477)
Tuberous sclerosis database (TSC2) RCV000042500 SCV000066291 not provided Tuberous sclerosis syndrome no assertion provided curation

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