Submissions for variant NM_000548.5(TSC2):c.3685C>T (p.Gln1229Ter)

dbSNP: rs45517306

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760363	SCV000890225	pathogenic	not provided	2022-07-19	criteria provided, single submitter	clinical testing	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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28968464, 25525159, 25498131, 25782670, 15798777, 17304050, 11112665, 31927531, 10205261, Wang2020[Case Report], 35712104, 26540169, 27535533)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001036695	SCV001200072	pathogenic	Tuberous sclerosis 2	2021-04-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1229*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 1112665, 28968464, Invitae). ClinVar contains an entry for this variant (Variation ID: 49270). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050).
Genome-Nilou Lab	RCV001036695	SCV002040980	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000760363	SCV005092631	pathogenic	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TSC2: PVS1, PM2, PS2:Moderate, PS4:Moderate
Tuberous sclerosis database (TSC2)	RCV000042529	SCV000066320	not provided	Tuberous sclerosis syndrome		no assertion provided	curation