Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001370391 | SCV001566868 | uncertain significance | Tuberous sclerosis 1 | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 818 of the TSC1 protein (p.Asn818Lys). This variant is not present in population databases (gnomAD no frequency). 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: 1060894). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC1 protein function. 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 | RCV002447486 | SCV002732110 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-04 | criteria provided, single submitter | clinical testing | The p.N818K variant (also known as c.2454C>G), located in coding exon 17 of the TSC1 gene, results from a C to G substitution at nucleotide position 2454. The asparagine at codon 818 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Fulgent Genetics, |
RCV002504619 | SCV002813351 | uncertain significance | Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II | 2021-10-27 | criteria provided, single submitter | clinical testing |