ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1281C>A (p.Ile427=)

gnomAD frequency: 0.00202  dbSNP: rs45478892
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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000174491 SCV000169107 benign not specified 2013-10-23 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.
Ambry Genetics RCV000163377 SCV000213917 likely benign Hereditary cancer-predisposing syndrome 2014-11-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Eurofins Ntd Llc (ga) RCV000174491 SCV000225800 likely benign not specified 2014-12-08 criteria provided, single submitter clinical testing
Invitae RCV000205713 SCV000261678 benign Tuberous sclerosis 2 2024-02-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000174491 SCV000305141 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000042948 SCV000395574 benign Tuberous sclerosis syndrome 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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000429983 SCV000511452 benign not provided 2016-07-13 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000174491 SCV000597591 likely benign not specified 2015-08-28 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000205713 SCV000677534 benign Tuberous sclerosis 2 2017-05-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000429983 SCV000697459 benign not provided 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The c.1281C>A (p.Ile427=) in TSC2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0022 (201/93004 chrs tested), predominantly in individuals of European descent (0.0032; 161/50172). This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000068). The variant of interest has been cited as Benign/Likely Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
CeGaT Center for Human Genetics Tuebingen RCV000429983 SCV001150687 likely benign not provided 2024-05-01 criteria provided, single submitter clinical testing TSC2: BP4, BP7, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000429983 SCV001470957 likely benign not provided 2022-09-12 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000205713 SCV002041145 benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000163377 SCV002532763 likely benign Hereditary cancer-predisposing syndrome 2021-03-12 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000174491 SCV002774064 benign not specified 2021-12-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002496678 SCV002804437 likely benign Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2022-04-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000205713 SCV004360859 benign Tuberous sclerosis 2 2022-09-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000042948 SCV004819245 benign Tuberous sclerosis syndrome 2024-02-05 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042948 SCV000066745 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000055284 SCV000083504 not provided Lymphangiomyomatosis no assertion provided curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000429983 SCV001808645 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000429983 SCV001922603 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000174491 SCV001975931 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000429983 SCV001979779 likely benign not provided no assertion criteria provided clinical testing

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