ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5220G>A (p.Trp1740Ter)

dbSNP: rs45517411
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493371 SCV000583283 pathogenic not provided 2017-05-25 criteria provided, single submitter clinical testing The W1740X nonsense variant in the TSC2 gene has been reported previously as a de novo change in an individual with TSC (Roberts et al., 2002; TSC2 LOVD). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 68 amino acids of the TSC2 protein are lost. The W1740X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Labcorp Genetics (formerly Invitae), Labcorp RCV000802438 SCV000942270 pathogenic Tuberous sclerosis 2 2024-09-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1740*) in the TSC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the TSC2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 12136241, 25782670). ClinVar contains an entry for this variant (Variation ID: 49363). This variant disrupts a region of the TSC2 protein in which other variant(s) (p.1784Alafs*, p.Phe1803Leufs*42) have been determined to be pathogenic (PMID: 9328481, 10205261, 24789117). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000802438 SCV002041025 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042623 SCV000066417 not provided Tuberous sclerosis syndrome no assertion provided curation

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