ClinVar Miner

Submissions for variant NM_000548.3(TSC2):c.3884-497_5045del

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459990 SCV000544475 pathogenic Tuberous sclerosis 2 2016-05-13 criteria provided, single submitter clinical testing This sequence change is a gross deletion of the genomic region involving exons 33-39 of the TSC2 gene. This deletion removes 4,721 nucleotides (c.3884-497_5045del) including a portion of intron 32, all of exons 33-38, and a portion of exon 39. While it is uncertain how this deletion affects mRNA splicing, it is expected to result in an absent or disrupted TSC2 protein with an in-frame deletion of ~390 amino acids. While this particular deletion has not been reported in the literature, in-frame deletions within this region have been described. Deletions of exons 34-35 and exons 34-36 (reported as 33-34 and 33-35, respectively, using the legacy exon numbering) have been reported in individuals affected with tuberous sclerosis complex (TSC) in the TSC LOVD database (PMID: 11112665). This gross deletion is expected to disrupt the C-terminal GAP domain of the TSC2 protein, which is important for tumor suppression function (PMID: 8799170, 9045618, 18466115, 15340059). For these reasons, this variant has been classified as Pathogenic.

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