ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2531T>C (p.Leu844Pro)

dbSNP: rs397515303
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001253278 SCV001428915 likely pathogenic Tuberous sclerosis 2 2017-12-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001253278 SCV003441708 pathogenic Tuberous sclerosis 2 2023-10-27 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 844 of the TSC2 protein (p.Leu844Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of tuberous sclerosis (PMID: 27859028, 35918040; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 64921). 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. This variant disrupts the p.Leu844 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been observed in individuals with TSC2-related conditions (PMID: 32461669), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000055123 SCV000083341 not provided Tuberous sclerosis syndrome no assertion provided curation

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