Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001383217 | SCV001582300 | pathogenic | Tuberous sclerosis 2 | 2020-07-20 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with tuberous sclerosis complex (PMID: 16114042, 10533067). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 49327). For these reasons, this variant has been classified as 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 1620 of the TSC2 protein (p.His1620Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Tuberous sclerosis database |
RCV000042587 | SCV000066381 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
| Prevention |
RCV004724772 | SCV005336116 | likely pathogenic | TSC2-related disorder | 2024-07-24 | no assertion criteria provided | clinical testing | The TSC2 c.4858C>T variant is predicted to result in the amino acid substitution p.His1620Tyr. This variant has been reported in two individuals with tuberous sclerosis and occurred de novo in one of the individuals (Table 2. Niida et al. 1999. PubMed ID: 10533067; Table 1. Rendtorff et al. 2005. PubMed ID: 16114042). This variant has also been reported to occur de novo in a prenatal specimen within a study investigating noninvasive prenatal diagnosis of tuberous sclerosis. The child was reported healthy at 2 1/2 years old in a follow-up (Yang et al. 2022. PubMed ID: 35429229). Different amino acid changes at the same codon, c.4859A>G (p.His1620Arg) and c.4859A>T (p.His1620Leu), have been reported as likely pathogenic in ClinVar (ClinVar IDs: 424510, 65243). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/49327/). This variant is interpreted as likely pathogenic. |