Submissions for variant NM_000548.5(TSC2):c.4174C>T (p.Gln1392Ter)

dbSNP: rs45517330

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660347	SCV000782409	pathogenic	Tuberous sclerosis 2	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000760365	SCV000890227	pathogenic	not provided	2018-12-18	criteria provided, single submitter	clinical testing	The Q1392X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (TSC) (Martin et al., 2017). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q1392X variant is not observed in large population cohorts (Lek et al., 2016).
Genome-Nilou Lab	RCV000660347	SCV002040990	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV004584339	SCV002578061	pathogenic	See cases	2021-12-20	criteria provided, single submitter	clinical testing	ACMG categories: PVS1,PS1,PP3,PP4,PP5
Labcorp Genetics (formerly Invitae), Labcorp	RCV000660347	SCV003443064	pathogenic	Tuberous sclerosis 2	2022-01-16	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 49806). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 32211034, 32313033). This sequence change creates a premature translational stop signal (p.Gln1392*) 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).
Neuberg Centre For Genomic Medicine, NCGM	RCV000660347	SCV005849194	pathogenic	Tuberous sclerosis 2		criteria provided, single submitter	clinical testing	The observed stop gained variant c.4174C>T(p.Gln1392Ter) in the TSC2 gene has been reported previously in individuals affected with tuberous sclerosis (Reyna-Fabián ME, et al., 2020; Ding Y, et al., 2020). This variant is absent in the gnomAD Exomes. It is submitted to ClinVar as Pathogenic by multiple submitters. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2)	RCV000043072	SCV000066871	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV000660347	SCV001364434	pathogenic	Tuberous sclerosis 2	2020-06-11	no assertion criteria provided	clinical testing