ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3791del (p.Pro1264fs) (rs137854001)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493012 SCV000581847 pathogenic not provided 2017-04-25 criteria provided, single submitter clinical testing The c.3791delC pathogenic variant in the TSC2 gene has been reported previously in association with TSC (TSC2 LOVD). The deletion causes a frameshift starting with codon Proline 1264, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 61 of the new reading frame, denoted p.Pro1264LeufsX61. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3791delC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Athena Diagnostics Inc RCV000493012 SCV000615903 pathogenic not provided 2016-09-21 criteria provided, single submitter clinical testing
Invitae RCV000702623 SCV000831483 pathogenic Tuberous sclerosis 2 2018-01-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1264Leufs*61) 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 individuals affected with tuberous sclerosis in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 49568). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042828 SCV000066624 not provided Tuberous sclerosis syndrome no assertion provided curation

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