ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.138_138+1del (rs137854117)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413387 SCV000491160 pathogenic not provided 2016-10-31 criteria provided, single submitter clinical testing The c.138_138+1delAG pathogenic variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (Ali et al., 2005 [reported as c.137_138delGA due to the use of alternative nomenclature]; Au et al., 2007; Kwiatkowski et al., 2015; TSC2 LOVD Database). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, 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.
Invitae RCV001056624 SCV001221077 pathogenic Tuberous sclerosis 2 2019-01-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the TSC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with tuberous sclerosis (PMID: 15595939, 25782670, 8990012, 9829910). ClinVar contains an entry for this variant (Variation ID: 49675). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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) RCV000042937 SCV000066734 not provided Tuberous sclerosis syndrome no assertion provided curation

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