ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3412C>T (p.Arg1138Ter)

dbSNP: rs45451497
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190075 SCV000243750 pathogenic not provided 2021-06-09 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32211034, 25525159, 25782670, 15798777, 16114042, 16981987, 15121797, 10533066, 28065512, 24271014, 33807840, 31927531, 30036593, 30185235, 27535533, 11112665, 33278787)
Athena Diagnostics Inc RCV000201090 SCV000255892 pathogenic Tuberous sclerosis 2 2015-08-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491678 SCV000579608 pathogenic Hereditary cancer-predisposing syndrome 2016-10-20 criteria provided, single submitter clinical testing The p.R1138* pathogenic mutation (also known as c.3412C>T), located in coding exon 29 of the TSC2 gene, results from a C to T substitution at nucleotide position 3412. This changes the amino acid from an arginine to a stop codon within coding exon 29. This pathogenic mutation has been reported in multiple unrelated individuals who met clinical criteria for tuberous sclerosis complex (TSC) (Mayer K et al. Hum. Mutat., 1999;14:401-11; Dabora SL et al. Am. J. Hum. Genet., 2001 Jan;68:64-80). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000201090 SCV000644437 pathogenic Tuberous sclerosis 2 2023-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1138*) 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: 10533066, 16981987). ClinVar contains an entry for this variant (Variation ID: 49257). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000190075 SCV001747141 pathogenic not provided 2021-06-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000201090 SCV002040973 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University RCV000201090 SCV002549156 pathogenic Tuberous sclerosis 2 2022-07-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002483040 SCV002788132 pathogenic Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2021-11-17 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042516 SCV000066307 not provided Tuberous sclerosis syndrome no assertion provided curation

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