Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189999 | SCV000243671 | pathogenic | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | Reported in individuals with tuberous sclerosis complex in published literature and in the Leiden Open-source Variation Database (LOVD) (Dombkowski et al., 2016; Fokkema et al., 2011); Published functional studies demonstrate a damaging effect: destabilized TSC1-TSC2 complex (Hoogeveen-Westerveld et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32320828, 21309039, 19747374, 21520333, 25452577, 32410215, 29655203) |
Athena Diagnostics Inc | RCV000201105 | SCV000255884 | likely pathogenic | Tuberous sclerosis 2 | 2015-09-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000201105 | SCV000955348 | likely pathogenic | Tuberous sclerosis 2 | 2021-02-24 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change destabilizes the TSC1-TSC2 complex (PMID: 21309039). This variant has been observed to be de novo individuals affected with TSC2-related disease (PMID: 21309039, 19747374). ClinVar contains an entry for this variant (Variation ID: 49725). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 804 of the TSC2 protein (p.Cys804Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. |
Genome- |
RCV000201105 | SCV002040955 | likely pathogenic | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Tuberous sclerosis database |
RCV000042990 | SCV000066788 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |