ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.133_136del (p.Leu45fs) (rs137854360)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484317 SCV000566310 pathogenic not provided 2017-08-02 criteria provided, single submitter clinical testing The c.133_136delCTGA deletion in the TSC2 gene has been reported multiple times in association withtuberous sclerosis complex (TSC) (Hung et al., 2006; TSC2 LOVD). The deletion causes a frameshift starting with codon Leucine 45, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Leu45GlufsX3. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret c.133_136delCTGA as a pathogenic variant.
Invitae RCV000554425 SCV000644229 pathogenic Tuberous sclerosis 2 2019-06-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu45Glufs*3) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 16981987, 21510812). ClinVar contains an entry for this variant (Variation ID: 49151). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042406 SCV000066196 not provided Tuberous sclerosis syndrome no assertion provided curation
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University RCV000554425 SCV001364421 pathogenic Tuberous sclerosis 2 2020-06-11 no assertion criteria provided clinical testing

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