ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3126G>C (p.Pro1042=)

dbSNP: rs36078782
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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118703 SCV000169131 benign not specified 2013-09-24 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 RCV000163284 SCV000213812 benign Hereditary cancer-predisposing syndrome 2014-12-23 criteria provided, single submitter clinical testing This alteration is classified as 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.
Invitae RCV000205029 SCV000261643 benign Tuberous sclerosis 2 2024-02-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000118703 SCV000305193 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000043004 SCV000395622 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.
Athena Diagnostics RCV000205029 SCV000677542 benign Tuberous sclerosis 2 2017-05-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000118703 SCV000918330 benign not specified 2018-06-05 criteria provided, single submitter clinical testing Variant summary: TSC2 c.3126G>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0042 in 276670 control chromosomes in the gnomAD database, including 26 homozygotes. The observed variant frequency is approximately 61-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3126G>C in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811310 SCV001471060 benign not provided 2023-11-17 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000205029 SCV002039291 benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000163284 SCV002533368 benign Hereditary cancer-predisposing syndrome 2020-08-04 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002504930 SCV002798852 likely benign Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2021-07-23 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000205029 SCV004016120 benign Tuberous sclerosis 2 2023-07-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000205029 SCV004360896 benign Tuberous sclerosis 2 2022-08-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000043004 SCV004817473 benign Tuberous sclerosis syndrome 2024-02-05 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043004 SCV000066802 not provided Tuberous sclerosis syndrome no assertion provided curation
Genetic Services Laboratory, University of Chicago RCV000118703 SCV000153118 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, Amsterdam University Medical Center RCV000118703 SCV001808729 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000118703 SCV001976077 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000118703 SCV001978126 benign not specified no assertion criteria provided clinical testing

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