ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.268C>T (p.Gln90Ter) (rs45517099)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000381969 SCV000329780 pathogenic not provided 2018-10-25 criteria provided, single submitter clinical testing The Q90X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (Choy 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. Therefore, we interpret Q90X as a pathogenic variant.
Ambry Genetics RCV000491603 SCV000579585 pathogenic Hereditary cancer-predisposing syndrome 2016-03-10 criteria provided, single submitter clinical testing Other acmg-defined mutation (i.e. initiation codon or gross deletion);Rarity in general population databases (dbsnp, esp, 1000 genomes);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Athena Diagnostics Inc RCV000381969 SCV000615894 pathogenic not provided 2017-07-31 criteria provided, single submitter clinical testing
Invitae RCV000707342 SCV000836434 pathogenic Tuberous sclerosis 2 2019-05-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln90*) 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 in individuals affected with tuberous sclerosis complex (PMID: 10735580, 17536269, 20498439, 20633017, 16981987, 11112665, 12111193). ClinVar contains an entry for this variant (Variation ID: 49738). 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) RCV000043003 SCV000066801 not provided Tuberous sclerosis syndrome no assertion provided curation

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