Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040743 | SCV001204332 | uncertain significance | Tuberous sclerosis 1 | 2024-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 428 of the TSC1 protein (p.Ala428Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with TSC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 135362). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV003162558 | SCV003911762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-01 | criteria provided, single submitter | clinical testing | The c.1282_1283delGCinsCT variant (also known as p.A428L), located in coding exon 11 of the TSC1 gene, results from an in-frame deletion of GC and insertion of CT at nucleotide positions 1282 to 1283. This results in the substitution of the alanine residue for a leucine residue at codon 428, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003474734 | SCV004204466 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-06-26 | criteria provided, single submitter | clinical testing | |
| ITMI | RCV000122187 | SCV000086404 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |