Submissions for variant NM_000548.5(TSC2):c.3442C>T (p.Gln1148Ter)

dbSNP: rs45477491

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478926	SCV000568292	pathogenic	not provided	2019-10-03	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 in large population cohorts (Lek et al., 2016); Reported previously in association with tuberous sclerosis (Jones et al., 1999; TSC2 LOVD); This variant is associated with the following publications: (PMID: 11208653, 25525159, 15121797, 10205261, 20633017)
Invitae	RCV000644112	SCV000765802	pathogenic	Tuberous sclerosis 2	2023-06-02	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1148*) 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 premature translational stop signal has been observed in individuals with tuberous sclerosis complex (PMID: 10205261, 11208653, 20633017). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 50087).
Genome-Nilou Lab	RCV000644112	SCV002040974	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000043353	SCV000067159	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055289	SCV000083509	not provided	Lymphangiomyomatosis; Tuberous sclerosis syndrome		no assertion provided	curation