ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4473del (p.Val1492fs) (rs397515023)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233034 SCV000285401 pathogenic Tuberous sclerosis 2 2016-01-21 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 34 of the TSC2 mRNA (c.4473delA), causing a frameshift at codon 1492. This creates a premature translational stop signal (p.Val1492Cysfs*84) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000279478 SCV000330402 pathogenic not provided 2016-04-19 criteria provided, single submitter clinical testing The c.4473delA pathogenic variant in the TSC2 gene has been reported previously in an individual with suspected tuberous sclerosis complex (TSC2 LOVD). The deletion causes a frameshift starting with codon Valine 1492, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 84 of the new reading frame, denoted p.Val1492CysfsX84. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.

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