Submissions for variant NM_000368.5(TSC1):c.106+15A>G

gnomAD frequency: 0.00187  dbSNP: rs80258442

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125622	SCV000169079	benign	not specified	2013-10-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000125622	SCV000269915	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	106+15A>G in intron 3 of TSC1: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 9.6% (17/178) of Japanese chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/projects/SN P; dbSNP rs80258442).
PreventionGenetics, part of Exact Sciences	RCV000125622	SCV000303839	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095335	SCV000478267	benign	Tuberous sclerosis 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000397239	SCV000478268	benign	Isolated focal cortical dysplasia type II	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589338	SCV000696598	benign	not provided	2016-05-26	criteria provided, single submitter	clinical testing	Variant summary: The TSC1 c.106+15A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant along with 5/5 in silico splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 630/119968 control chromosomes (26 homozygotes), predominantly observed in the East Asian subpopulation (25 homozygotes) at a frequency of 0.0705565 (601/8518). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic TSC1 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in populations of East Asian origin. In addition, one clinical diagnostic laboratory classified this variant as Benign. Taken together, this variant is classified as Benign.
Invitae	RCV001095335	SCV001730504	benign	Tuberous sclerosis 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001095335	SCV002041165	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001095335	SCV004016074	benign	Tuberous sclerosis 1	2023-07-07	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC1)	RCV000041984	SCV000065763	not provided	Tuberous sclerosis syndrome		no assertion provided	curation