ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3797dup (p.Pro1267fs)

dbSNP: rs796053505
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190062 SCV000243737 likely pathogenic not provided 2024-09-05 criteria provided, single submitter clinical testing Reported in both an affected and in an unaffected relative of individuals previously tested at GeneDx; Frameshift 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 (gnomAD); This variant is associated with the following publications: (PMID: 29655203, 21520333, 34308104, 33084842, 29926239, 10205261, 17304050)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000190062 SCV000610282 likely pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000802435 SCV000942267 pathogenic Tuberous sclerosis 2 2024-05-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1267Alafs*55) 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 TSC2- related disease (PMID: 21520333, 29926239). ClinVar contains an entry for this variant (Variation ID: 207775). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000802435 SCV002040985 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV004948204 SCV005526020 pathogenic Hereditary cancer-predisposing syndrome 2024-07-29 criteria provided, single submitter clinical testing The c.3797dupT pathogenic mutation, located in coding exon 30 of the TSC2 gene, results from a duplication of T at nucleotide position 3797, causing a translational frameshift with a predicted alternate stop codon (p.P1267Afs*55). This alteration was identified in a cohort of patients with epilepsy and/or neurodevelopmental disorders (Lindy AS et al. Epilepsia, 2018 May;59:1062-1071). This alteration was also identified in a patient with infantile spasms and a hypomelanotic macule (Caylor RC et al. Neurogenetics, 2018 Aug;19:205-213). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

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