ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5214del (p.Lys1739fs)

dbSNP: rs397515139
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486348 SCV000567158 pathogenic not provided 2015-07-13 criteria provided, single submitter clinical testing The c.5214delC deletion in the TSC2 gene causes a frameshift starting with codon Lysine 1739, changesthis amino acid to a Serine residue and creates a premature Stop codon at position 87 of the new readingframe, denoted p.Lys1739SerfsX87. It was not observed in approximately 6,500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a commonbenign variant in these populations. This variant is predicted to cause loss of normal protein function asthe last 69 amino acids of the protein are replaced by 86 aberrant residues. Although this variant has notbeen previously reported to our knowledge, we interpret it as pathogenic.
Invitae RCV002525795 SCV003205871 pathogenic Tuberous sclerosis 2 2022-06-12 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the TSC2 gene (p.Lys1739Serfs*87). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the TSC2 protein and extend the protein by 17 additional amino acid residues. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TSC2 protein in which other variant(s) (p.Arg1743Gln) have been determined to be pathogenic (PMID: 10732801, 16114042, 18854862, 20165957, 21309039). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 419391). 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).

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