ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5281_5296del (p.Ser1761fs) (rs1064792923)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464189 SCV000544587 pathogenic Tuberous sclerosis 2 2017-10-16 criteria provided, single submitter clinical testing This sequence change deletes 16 nucleotides in exon 42 of the TSC2 mRNA (c.5281_5296delTCCAACCCCAGCCTAC), causing a frameshift at codon 1761. This creates a premature translational stop signal in the last exon of the TSC2 mRNA (p.Ser1761Leufs*60). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acids of the TSC2 protein. This variant has been reported in an individual with tuberous sclerosis complex (TSC) in the Leiden Open-source Variation Database (PMID: 21520333, 25498131). Multiple frameshift variants including c.5340_5371del (p.1784Alafs*?) and c.5405_5408dup (p.Phe1803Leufs*42), located downstream of this variant have been reported as disease-causing de novo variants in individuals affected with TSC (PMID: 10205261, 9328481, 24789117), suggesting that frameshift variants affecting the very C-terminal of TSC2 impact protein function and cause disease. For these reasons, this variant has been classified as Pathogenic.

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