ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2410T>C (p.Cys804Arg)

dbSNP: rs137853995
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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-Nilou Lab RCV000201105 SCV002040955 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042990 SCV000066788 not provided Tuberous sclerosis syndrome no assertion provided curation

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