Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV001508405 | SCV001714536 | likely pathogenic | not provided | 2020-04-10 | criteria provided, single submitter | clinical testing | PM2, PM6, PP1, PP4 |
| Labcorp Genetics |
RCV001852888 | SCV002312810 | likely pathogenic | Tuberous sclerosis 2 | 2021-09-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 1595 of the TSC2 protein (p.Gly1595Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This missense change has been observed in individuals with tuberous sclerosis complex (PMID: 31927531; Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 49464). |
| Ambry Genetics | RCV003162357 | SCV003859983 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-23 | criteria provided, single submitter | clinical testing | The p.G1595R variant (also known as c.4783G>A), located in coding exon 36 of the TSC2 gene, results from a G to A substitution at nucleotide position 4783. This alteration has been observed in at least two individuals with a personal and/or family history that is consistent with TSC2-related disease (Jiangyi W et al. Aging (Albany NY), 2020 01;12:756-766; personal communication). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The glycine at codon 1595 is replaced by arginine, an amino acid with dissimilar 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 majority of available evidence to date, this variant is likely to be pathogenic. |
| Tuberous sclerosis database |
RCV000042724 | SCV000066519 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |