ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1840G>C (p.Ala614Pro)

dbSNP: rs397515199
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000227968 SCV000285259 pathogenic Tuberous sclerosis 2 2022-01-12 criteria provided, single submitter clinical testing This variant disrupts the p.Ala614 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10205261, 11741832, 15483652, 21309039, 32313033). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 614 of the TSC2 protein (p.Ala614Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with tuberous sclerosis complex (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 237972). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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