ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3797dup (p.Pro1267fs) (rs796053505)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190062 SCV000243737 pathogenic not provided 2018-06-12 criteria provided, single submitter clinical testing The c.3797dupT variant in the TSC2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3797dupT variant causes a frameshift starting with codon Proline 1267, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 55 of the new reading frame, denoted p.Pro1267AlafsX55. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3797dupT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3797dupT as a pathogenic variant.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000190062 SCV000610282 likely pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing
Invitae RCV000802435 SCV000942267 pathogenic Tuberous sclerosis 2 2019-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1267Alafs*55) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature and in the Leiden Open-source Variation Database (PMID: 21520333) in families affected with TSC2- related disease (PMID: 29926239). ClinVar contains an entry for this variant (Variation ID: 207775). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.

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