ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.496C>T (p.Gln166Ter)

dbSNP: rs45517111
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000351808 SCV000329782 pathogenic not provided 2016-09-27 criteria provided, single submitter clinical testing The Q166X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (Niida et al., 1999; TSC2 LOVD). 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. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV002513629 SCV003441704 pathogenic Tuberous sclerosis 2 2022-10-23 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln166*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 10533067). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 49819).
Tuberous sclerosis database (TSC2) RCV000043085 SCV000066884 not provided Tuberous sclerosis syndrome no assertion provided curation

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