ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2117T>C (p.Leu706Pro)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MGZ Medical Genetics Center RCV002290060 SCV002581701 uncertain significance Tuberous sclerosis 2 2022-08-01 criteria provided, single submitter clinical testing
GeneDx RCV004721038 SCV005327936 likely pathogenic not provided 2024-03-19 criteria provided, single submitter clinical testing 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: 27859028)
Labcorp Genetics (formerly Invitae), Labcorp RCV002290060 SCV005837260 likely pathogenic Tuberous sclerosis 2 2024-03-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 706 of the TSC2 protein (p.Leu706Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 27859028). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1709718). 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 TSC2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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