Submissions for variant NM_000548.5(TSC2):c.5202T>C (p.Asp1734=)

gnomAD frequency: 0.35806  dbSNP: rs1748

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118713	SCV000200862	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Asp1734Asp in exon 41 of TSC2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 36.6% (1607/4396) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1748).
Ambry Genetics	RCV000162957	SCV000213445	benign	Hereditary cancer-predisposing syndrome	2014-11-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV000118713	SCV000305245	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000043161	SCV000395678	benign	Tuberous sclerosis syndrome	2018-01-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588289	SCV000605460	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588289	SCV000697476	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.5202T>C (p.Asp1734Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 22671/120414 control chromosomes (3647 homozygotes) at a frequency of 0.1882754, which is approximately 2738 times the estimated maximal expected allele frequency of a pathogenic TSC2 variant (0.0000688), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
Invitae	RCV001510590	SCV001717663	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000588289	SCV001894809	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001510590	SCV002039925	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001510590	SCV004016095	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001510590	SCV004360943	benign	Tuberous sclerosis 2	2019-03-28	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000043161	SCV000066960	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055450	SCV000083671	not provided	Lymphangiomyomatosis; Tuberous sclerosis syndrome		no assertion provided	curation
Genetic Services Laboratory, University of Chicago	RCV000118713	SCV000153128	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118713	SCV001930209	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118713	SCV001975848	benign	not specified		no assertion criteria provided	clinical testing