Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002316686 | SCV000850316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-09 | criteria provided, single submitter | clinical testing | The p.R680G variant (also known as c.2038C>G), located in coding exon 18 of the TSC2 gene, results from a C to G substitution at nucleotide position 2038. The arginine at codon 680 is replaced by glycine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6274 samples (12548 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000815171 | SCV000955618 | uncertain significance | Tuberous sclerosis 2 | 2022-05-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 589454). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 680 of the TSC2 protein (p.Arg680Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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. |
Genome- |
RCV000815171 | SCV002040670 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |