Submissions for variant NM_000548.5(TSC2):c.1096G>T (p.Glu366Ter)

dbSNP: rs45517148

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497801	SCV000589549	pathogenic	not provided	2017-06-20	criteria provided, single submitter	clinical testing	The E366X nonsense variant in the TSC2 gene has been reported multiple times previously in association with TSC (Dabora et al., 2001; TSC2 LOVD). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E366X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001194675	SCV003804252	pathogenic	Tuberous sclerosis 2	2023-01-23	criteria provided, single submitter	clinical testing
OMIM	RCV000055263	SCV000033456	pathogenic	Lymphangiomyomatosis	2000-05-23	no assertion criteria provided	literature only
Tuberous sclerosis database (TSC2)	RCV000042986	SCV000066784	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055263	SCV000083482	not provided	Lymphangiomyomatosis		no assertion provided	curation
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV001194675	SCV001364416	pathogenic	Tuberous sclerosis 2	2020-06-11	no assertion criteria provided	clinical testing
deCODE genetics, Amgen	RCV001194675	SCV004022271	likely pathogenic	Tuberous sclerosis 2	2023-07-21	no assertion criteria provided	research	The variant NM_000548.5:c.1096G>T (chr16:2060790) in TSC2 was detected in 1 heterozygote out of 58K WGS Icelanders (MAF= 0,001%). This variant has been reported in ClinVar previously as pathogenic. Based on ACMG criteria (PVS1, PM2) this variant classifies as likely pathogenic.