Submissions for variant NM_000548.5(TSC2):c.826_827del (p.Met276fs)

dbSNP: rs137853977

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000312270	SCV000232977	pathogenic	not provided	2015-01-09	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000180518	SCV000255920	pathogenic	Tuberous sclerosis 2	2014-09-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000312270	SCV000329784	pathogenic	not provided	2021-11-15	criteria provided, single submitter	clinical testing	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: 26014699, 10735580, 28087349, 10533067, 29975249, 29432982, 31586081, 11112665, 16114042)
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000180518	SCV000782396	pathogenic	Tuberous sclerosis 2	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000180518	SCV001220719	pathogenic	Tuberous sclerosis 2	2023-12-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Met276Valfs*61) 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 tuberous sclerosis complex (PMID: 10533067, 11112665, 16114042). ClinVar contains an entry for this variant (Variation ID: 49447). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000180518	SCV002040922	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000312270	SCV002563281	pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing	TSC2: PVS1, PM2, PS4:Moderate
3billion	RCV000180518	SCV002572873	pathogenic	Tuberous sclerosis 2	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000049447 / PMID: 10533067). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000180518	SCV004697501	pathogenic	Tuberous sclerosis 2		criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042707	SCV000066502	not provided	Tuberous sclerosis syndrome		no assertion provided	curation