ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3598C>T (p.Arg1200Trp) (rs45438205)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190021 SCV000243693 pathogenic not provided 2018-08-22 criteria provided, single submitter clinical testing The R1200W variant in the TSC2 gene has been published in association with both sporadic and familial TSC (Wilson et al., 1996; Au et al., 1998; Wentink et al., 2012; TSC2 LOVD). While some individuals with the R1200W variant are reported to meet clinical diagnostic criteria for definite TSC, others have been reported to have a milder clinical presentation characterized primarily by the presence of skin findings with or without epilepsy (Wentink et al., 2012). Functional studies indicate that R1200W disrupts the function of the TSC1-TSC2 complex (Hoogeveen-Westerveld et al., 2011; Wentink et al., 2012). Therefore, R1200W is interpreted as a pathogenic variant.
Athena Diagnostics Inc RCV000190880 SCV000255893 pathogenic Tuberous sclerosis 2 2014-05-20 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000190021 SCV000337423 pathogenic not provided 2015-11-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000190021 SCV000615900 pathogenic not provided 2014-05-20 criteria provided, single submitter clinical testing
Invitae RCV000190880 SCV000765896 pathogenic Tuberous sclerosis 2 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1200 of the TSC2 protein (p.Arg1200Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature to segregate with tuberous sclerosis complex and a wide range of phenotypes including some milder cases in many families (PMID: 8824881, 22867869, 28149746, 21332470, 25039834, 18792920, 9463313). This variant is also known as c.3616C>T (p.Arg1199Trp). ClinVar contains an entry for this variant (Variation ID: 49770). Experimental studies have shown that this missense change results in an unstable protein and disrupts the normal function of TSC2 as a regulator of cellular growth and proliferation (PMID: 21309039, 21332470). For these reasons, this variant has been classified as Pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000190880 SCV000782406 pathogenic Tuberous sclerosis 2 2016-11-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000190021 SCV001247496 pathogenic not provided 2017-05-01 criteria provided, single submitter clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University RCV000190880 SCV001423570 pathogenic Tuberous sclerosis 2 2020-07-10 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043035 SCV000066834 not provided Tuberous sclerosis syndrome no assertion provided curation
GeneReviews RCV000190880 SCV000245753 pathogenic Tuberous sclerosis 2 2015-09-03 no assertion criteria provided literature only

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