Submissions for variant NM_000548.5(TSC2):c.3750C>G (p.Tyr1250Ter)

dbSNP: rs45517308

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000042810	SCV000967770	pathogenic	Tuberous sclerosis syndrome	2018-04-20	criteria provided, single submitter	clinical testing	The p.Tyr1250X variant in TSC2 has been reported in 5 individuals with tuberous sclerosis complex (TSC; Dabora 2001, Tyburczy 2014, Cai 2017, Tuberous sclerosis LOVD database: http://chromium.lovd.nl/LOVD2/TSC) and was absent from large pop ulation studies. This nonsense variant leads to a premature termination codon at position 1250, which is predicted to lead to a truncated or absent protein. Het erozygous loss of function of the TSC2 gene is an established disease mechanism in individuals with TSC. In summary, this variant meets criteria to be classifie d as pathogenic for TSC in an autosomal dominant manner based upon presence in m ultiple affected individuals, absence from the general population and predicted impact to protein. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Moderate.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV002266913	SCV002549155	pathogenic	Tuberous sclerosis 2	2022-07-19	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV002266913	SCV003823691	pathogenic	Tuberous sclerosis 2	2021-12-13	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042810	SCV000066606	not provided	Tuberous sclerosis syndrome		no assertion provided	curation