Submissions for variant NM_000548.5(TSC2):c.1513C>T (p.Arg505Ter) (rs45517179)

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Total submissions: 6

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000517734	SCV000615884	pathogenic	not provided	2016-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV000013204	SCV000822814	pathogenic	Tuberous sclerosis 2	2018-11-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg505*) 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 reported in individuals affected with tuberous sclerosis complex (PMID: 8824881, 16981987, 10205261, 9463313, 16114042, 11112665). ClinVar contains an entry for this variant (Variation ID: 12396). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768350	SCV000899048	pathogenic	Lymphangiomyomatosis; Focal cortical dysplasia type II; Tuberous sclerosis 2	2017-12-04	criteria provided, single submitter	clinical testing	TSC2 NM_000548.4 exon 15 p.Arg505* (c.1513C>T): This variant has been reported in the literature in at least 10 individuals with Tuberous sclerosis (Wilson 1996 PMID:8824881, Jones 1999 PMID:10205261, Mayer 1999 PMID:10533066, Dabora 2001 PMID:11112665, Rendtorff 2005 PMID:16114042, Hung 2006 PMID:16981987, Au 2007 PMID:17304050). This variant is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant creates a premature stop at this codon which results in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Rosset 2017 PMID:28222202). In summary, this variant is classified as pathogenic.
OMIM	RCV000013204	SCV000033451	pathogenic	Tuberous sclerosis 2	1999-12-01	no assertion criteria provided	literature only
Tuberous sclerosis database (TSC2)	RCV000043399	SCV000067205	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055539	SCV000083762	not provided	Lymphangiomyomatosis		no assertion provided	curation

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