Submissions for variant NM_000548.5(TSC2):c.4909AAG[1] (p.Lys1638del)

dbSNP: rs137854261

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000517321	SCV000615915	pathogenic	not provided	2014-11-20	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset. Found in multiple de novo cases.
Invitae	RCV000201053	SCV000765953	pathogenic	Tuberous sclerosis 2	2023-10-16	criteria provided, single submitter	clinical testing	This variant, c.4912_4914del, results in the deletion of 1 amino acid(s) of the TSC2 protein (p.Lys1638del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with tuberous sclerosis complex (PMID: 17304050, 20165957, 21520333, 22867869). In at least one individual the variant was observed to be de novo. This variant is also known as c.4909_4911delAAG. ClinVar contains an entry for this variant (Variation ID: 49893). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV000201053	SCV001423572	likely pathogenic	Tuberous sclerosis 2	2020-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000517321	SCV001823756	pathogenic	not provided	2020-08-17	criteria provided, single submitter	clinical testing	Reported multiple times as a pathogenic variant is association with tuberous sclerosis complex (Au et al., 2007, Qin et al, 2010, vanEeghen et al., 2013; TSC2 LOVD); Not observed in large population cohorts (Lek et al., 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32555378, 22867869, 20165957, 17304050, 31855466)
CeGaT Center for Human Genetics Tuebingen	RCV000517321	SCV001961554	pathogenic	not provided	2021-07-01	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000043159	SCV000066507	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000043159	SCV000066958	not provided	Tuberous sclerosis syndrome		no assertion provided	curation