Submissions for variant NM_000548.5(TSC2):c.1959_1960del (p.Gly654fs)

dbSNP: rs137854144

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000201097	SCV000255878	pathogenic	Tuberous sclerosis 2	2013-01-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001555731	SCV001777190	pathogenic	not provided	2021-05-13	criteria provided, single submitter	clinical testing	Reported as c.1957-1958delAG due the use of alternative nomenclature in association with tuberous sclerosis complex in the published literature (Li et al., 2011); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21811971)
Genome-Nilou Lab	RCV000201097	SCV002040944	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000201097	SCV002243232	pathogenic	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly654Leufs*2) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 21811971). This variant is also known as c.1957-1958delAG. ClinVar contains an entry for this variant (Variation ID: 65311). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2)	RCV000055533	SCV000083756	not provided	Tuberous sclerosis syndrome		no assertion provided	curation