Submissions for variant NM_000548.5(TSC2):c.3532C>T (p.Gln1178Ter)

dbSNP: rs45517297

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481829	SCV000568293	pathogenic	not provided	2017-02-03	criteria provided, single submitter	clinical testing	The Q1178X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis (Niida et al., 1999; TSC2 LOVD). The Q1178X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, the presence of Q1178X is consistent with the diagnosis of TSC in this individual.
Invitae	RCV000694582	SCV000823033	pathogenic	Tuberous sclerosis 2	2022-11-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 49263). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 10533067). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1178*) 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).
Genome-Nilou Lab	RCV000694582	SCV002040976	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042522	SCV000066313	not provided	Tuberous sclerosis syndrome		no assertion provided	curation