Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013644 | SCV001174257 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-15 | criteria provided, single submitter | clinical testing | The p.P645L variant (also known as c.1934C>T), located in coding exon 13 of the TSC1 gene, results from a C to T substitution at nucleotide position 1934. The proline at codon 645 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001496179 | SCV001700872 | likely benign | Tuberous sclerosis 1 | 2024-12-29 | criteria provided, single submitter | clinical testing | |
| St. |
RCV001554285 | SCV001775527 | uncertain significance | Tuberous sclerosis syndrome | 2021-08-05 | criteria provided, single submitter | clinical testing | The TSC1 c.1934C>T (p.Pro645Leu) missense change has a maximum subpopulation frequency of 0.00088% in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/9-135781031-G-A). Six of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, PP3. |
| Genome- |
RCV001496179 | SCV002040079 | likely benign | Tuberous sclerosis 1 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001554285 | SCV004824820 | uncertain significance | Tuberous sclerosis syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 645 of the TSC1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has been identified in 1/251400 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |