Submissions for variant NM_000548.5(TSC2):c.133_136del (p.Leu45fs) (rs137854360)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484317	SCV000566310	pathogenic	not provided	2017-08-02	criteria provided, single submitter	clinical testing	The c.133_136delCTGA deletion in the TSC2 gene has been reported multiple times in association withtuberous sclerosis complex (TSC) (Hung et al., 2006; TSC2 LOVD). The deletion causes a frameshift starting with codon Leucine 45, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Leu45GlufsX3. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret c.133_136delCTGA as a pathogenic variant.
Invitae	RCV000554425	SCV000644229	pathogenic	Tuberous sclerosis 2	2019-06-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu45Glufs*3) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 16981987, 21510812). ClinVar contains an entry for this variant (Variation ID: 49151). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2)	RCV000042406	SCV000066196	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University	RCV000554425	SCV001364421	pathogenic	Tuberous sclerosis 2	2020-06-11	no assertion criteria provided	clinical testing