Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000644148 | SCV000765838 | uncertain significance | Tuberous sclerosis 2 | 2023-07-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 535918). 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 TSC2 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. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1419 of the TSC2 protein (p.Gln1419His). |
Gene |
RCV001771883 | SCV002002232 | uncertain significance | not provided | 2020-06-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV000644148 | SCV002040814 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002331188 | SCV002631666 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.Q1419H variant (also known as c.4257G>C), located in coding exon 33 of the TSC2 gene, results from a G to C substitution at nucleotide position 4257. The glutamine at codon 1419 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |