Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000817575 | SCV000958144 | pathogenic | Tuberous sclerosis 2 | 2024-11-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1451Profs*73) 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 (PMID: 32211034). ClinVar contains an entry for this variant (Variation ID: 65040). For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV000817575 | SCV004100452 | likely pathogenic | Tuberous sclerosis 2 | criteria provided, single submitter | clinical testing | The frameshift duplication p.R1451Pfs*73 in TSC2 (NM_000548.5) has been reported in ClinVar as Pathogenic. The p.R1451Pfs*73 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The frame shifted sequence continues 73 residues until a stop codon is reached. For these reasons, this variant has been classified as Likely Pathogenic. | |
| Ambry Genetics | RCV005298443 | SCV005963859 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-01-23 | criteria provided, single submitter | clinical testing | The c.4351dupC pathogenic mutation, located in coding exon 33 of the TSC2 gene, results from a duplication of C at nucleotide position 4351, causing a translational frameshift with a predicted alternate stop codon (p.R1451Pfs*73). This variant was reported in individual(s) with features consistent with Tuberous sclerosis complex (Chung CWT et al. Mol Genet Genomic Med, 2024 Oct;12:e70017; Ding Y et al. Seizure, 2021 Oct;91:273-277). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Tuberous sclerosis database |
RCV000055246 | SCV000083465 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |