Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000201015 | SCV000255848 | pathogenic | Tuberous sclerosis 1 | 2014-09-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000201015 | SCV001578947 | pathogenic | Tuberous sclerosis 1 | 2024-04-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg420Glyfs*20) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 10533069, 26493680). ClinVar contains an entry for this variant (Variation ID: 48753). For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000201015 | SCV002041053 | pathogenic | Tuberous sclerosis 1 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000042000 | SCV004121990 | pathogenic | Tuberous sclerosis syndrome | 2023-10-23 | criteria provided, single submitter | clinical testing | Variant summary: TSC1 c.1257delC (p.Arg420GlyfsX20) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251098 control chromosomes. c.1257delC has been reported in the literature in at-least four individuals affected with Tuberous Sclerosis Complex (examples, Santos_2015, Verhoef_1999). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26493680, 10330349). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Ambry Genetics | RCV004678602 | SCV005174505 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | The c.1257delC pathogenic mutation, located in coding exon 10 of the TSC1 gene, results from a deletion of one nucleotide at nucleotide position 1257, causing a translational frameshift with a predicted alternate stop codon (p.R420Gfs*20). This variant has been observed in multiple individuals with features associated with tuberous sclerosis complex (TSC) (Bénit P et al. Hum Mutat, 1999;14:428-32; Santos L et al. Pathol Res Pract, 2015 Dec;211:1025-9; Atli EI et al. Intern Med J, 2022 Jul;52:1174-1184). 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. |
| Tuberous sclerosis database |
RCV000042000 | SCV000065781 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |