ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5252_5259+19del

dbSNP: rs137854397
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201086 SCV000255915 pathogenic Tuberous sclerosis 2 2013-05-03 criteria provided, single submitter clinical testing
Invitae RCV000201086 SCV000944719 pathogenic Tuberous sclerosis 2 2023-10-16 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 41 (c.5252_5252+19) of the TSC2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with tuberous sclerosis complex (PMID: 11112665, 21520333, 25498131). ClinVar contains an entry for this variant (Variation ID: 49366). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant disrupts a region of the TSC2 protein in which other variant(s) (p.Ser1761Leufs*60) have been determined to be pathogenic (Invitae). 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.
GeneDx RCV001557698 SCV001779505 pathogenic not provided 2020-04-27 criteria provided, single submitter clinical testing Deletions involving coding exons of this gene are a known mechanism of disease (Stenson et al., 2014); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27406250, 11112665, 16981987)
Genome-Nilou Lab RCV000201086 SCV002041029 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042626 SCV000066420 not provided Tuberous sclerosis syndrome no assertion provided curation

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