ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4849+5_4849+32del

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002730333 SCV003015072 uncertain significance Tuberous sclerosis 2 2023-08-24 criteria provided, single submitter clinical testing This sequence change falls in intron 37 of the TSC2 gene. It does not directly change the encoded amino acid sequence of the TSC2 protein. It affects a nucleotide within the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). ClinVar contains an entry for this variant (Variation ID: 1970032). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency).
All of Us Research Program, National Institutes of Health RCV004007569 SCV004838191 uncertain significance Tuberous sclerosis syndrome 2023-11-20 criteria provided, single submitter clinical testing This variant deletes 28 nucleotides in intron 37 of the TSC2 gene. Splice site prediction tools predict that this variant may impact on RNA splicingTo our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004067778 SCV005036644 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-01 criteria provided, single submitter clinical testing The c.4849+5_4849+32del28 intronic variant, located in intron 36 of the TSC2 gene, results from a deletion of 28 nucleotides within intron 36 of the TSC2 gene. The nucleotide positions in this region are well conserved in available vertebrate species on limited alignment. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004593055 SCV005078583 uncertain significance not provided 2023-12-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge

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