Submissions for variant NM_000548.5(TSC2):c.3206_3207del (p.Val1069fs)

dbSNP: rs137854076

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000201154	SCV000255890	pathogenic	Tuberous sclerosis 2	2013-06-14	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727088	SCV000705518	pathogenic	not provided	2017-02-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000201154	SCV002040969	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000201154	SCV002572983	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: VCV000049246 / PMID: 12111193). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Ambry Genetics	RCV002321535	SCV002610400	pathogenic	Hereditary cancer-predisposing syndrome	2018-09-14	criteria provided, single submitter	clinical testing	The c.3206_3207delTG pathogenic mutation, located in coding exon 27 of the TSC2 gene, results from a deletion of two nucleotides at nucleotide positions 3206 to 3207, causing a translational frameshift with a predicted alternate stop codon (p.V1069Dfs*98). This alteration was detected in one individual who fulfilled diagnostic criteria for Tuberous Sclerosis Complex (TSC) (Langkau N et al. Eur. J. Pediatr., 2002 Jul;161:393-402) and as a de novo occurrence in an infant with seizures and hypomelanotic macules (Li W et al. J. Neurogenet. Oct;30:285-287). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000201154	SCV003441711	pathogenic	Tuberous sclerosis 2	2024-11-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val1069Aspfs*98) 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: 12111193). This variant is also known as 3224-3225delTG. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000727088	SCV004033430	pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	TSC2: PVS1, PM2, PS4:Moderate
Tuberous sclerosis database (TSC2)	RCV000042505	SCV000066296	not provided	Tuberous sclerosis syndrome		no assertion provided	curation