ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1111C>T (p.Gln371Ter) (rs45469099)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000644081 SCV000765771 pathogenic Tuberous sclerosis 2 2017-11-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln371*) 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 reported to be de novo in an individual affected with tuberous sclerosis (PMID: 9881533) and has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 49142). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000760655 SCV000890547 pathogenic not provided 2018-07-27 criteria provided, single submitter clinical testing The Q371X nonsense variant in the TSC2 gene has been reported previously in association with TSC, including as a de novo change (Rendtorff et al., 2005 [reported as Q370X due to the use of alternate nomenclature]; Nallasamy et al., 2017; TSC2 LOVD). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the Q371X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, the Q371X variant is considered a pathogenic variant.
Tuberous sclerosis database (TSC2) RCV000042397 SCV000066187 not provided Tuberous sclerosis syndrome no assertion provided curation

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