ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3750C>G (p.Tyr1250Ter)

dbSNP: rs45517308
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000042810 SCV000967770 pathogenic Tuberous sclerosis syndrome 2018-04-20 criteria provided, single submitter clinical testing The p.Tyr1250X variant in TSC2 has been reported in 5 individuals with tuberous sclerosis complex (TSC; Dabora 2001, Tyburczy 2014, Cai 2017, Tuberous sclerosis LOVD database: http://chromium.lovd.nl/LOVD2/TSC) and was absent from large pop ulation studies. This nonsense variant leads to a premature termination codon at position 1250, which is predicted to lead to a truncated or absent protein. Het erozygous loss of function of the TSC2 gene is an established disease mechanism in individuals with TSC. In summary, this variant meets criteria to be classifie d as pathogenic for TSC in an autosomal dominant manner based upon presence in m ultiple affected individuals, absence from the general population and predicted impact to protein. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Moderate.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University RCV002266913 SCV002549155 pathogenic Tuberous sclerosis 2 2022-07-19 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002266913 SCV003823691 pathogenic Tuberous sclerosis 2 2021-12-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002266913 SCV005838267 pathogenic Tuberous sclerosis 2 2024-06-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1250*) 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 variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 11112665, 36232477). ClinVar contains an entry for this variant (Variation ID: 49550). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042810 SCV000066606 not provided Tuberous sclerosis syndrome no assertion provided curation

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