Submissions for variant NM_000548.5(TSC2):c.1372C>T (p.Arg458Ter)

dbSNP: rs45517169

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000201131	SCV000255873	pathogenic	Tuberous sclerosis 2	2014-06-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000441085	SCV000516760	pathogenic	not provided	2020-11-04	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29925043, 28065512, 25782670, 32211034, 10090883, 11112665, 17304050, 25525159, 26563443, 21510812, 20633017, 15121797)
Invitae	RCV000201131	SCV000644237	pathogenic	Tuberous sclerosis 2	2023-07-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg458*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 10090883, 11112665, 15121797, 20633017, 21510812, 21520333, 25782670, 28065512). ClinVar contains an entry for this variant (Variation ID: 49153). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000624878	SCV000741022	pathogenic	Inborn genetic diseases	2016-08-04	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000042408	SCV000928333	pathogenic	Tuberous sclerosis syndrome	2019-07-17	criteria provided, single submitter	clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV000201131	SCV001364422	pathogenic	Tuberous sclerosis 2	2022-07-19	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000201131	SCV002040934	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000441085	SCV002818246	pathogenic	not provided	2022-12-17	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042408	SCV000066199	not provided	Tuberous sclerosis syndrome		no assertion provided	curation