ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.2829C>T (p.Ala943=) (rs4962081)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118693 SCV000169094 benign not specified 2015-03-04 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,Partners HealthCare Personalized Medicine RCV000118693 SCV000205282 benign not specified 2013-02-21 criteria provided, single submitter clinical testing Ala943Ala in exon 22 of TSC1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 9.1% (399/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs4962081).
Ambry Genetics RCV000162946 SCV000213433 benign Hereditary cancer-predisposing syndrome 2014-11-19 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000118693 SCV000227885 benign not specified 2014-07-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000118693 SCV000303866 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000576543 SCV000478189 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 Clinical Services Laboratory,Illumina RCV000370584 SCV000478190 benign 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.
Athena Diagnostics Inc RCV000576543 SCV000677528 benign Tuberous sclerosis 1 2017-04-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590200 SCV000696607 benign not provided 2016-05-26 criteria provided, single submitter clinical testing Variant summary: The TSC1 c.2829C>T (p.Ala943Ala) 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 along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 9206/121392 control chromosomes (457 homozygotes), predominantly observed in the Latino, (143 homozygotes) subpopulation at a frequency of 0.1558127 (1804/11578). 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 the populations of Latino origin. In addition, multiple clinical diagnostic laboratories classified this variant as Benign. Taken together, this variant is classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282237 SCV000884749 benign none provided 2020-08-27 criteria provided, single submitter clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University RCV000576543 SCV001430708 likely benign Tuberous sclerosis 1 2020-07-10 criteria provided, single submitter clinical testing
Invitae RCV000576543 SCV001726098 benign Tuberous sclerosis 1 2020-11-28 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC1) RCV000042257 SCV000066044 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC1) RCV000054906 SCV000083121 not provided Urinary bladder cancer no assertion provided curation
Tuberous sclerosis database (TSC1) RCV000055028 SCV000083246 not provided Lymphangiomyomatosis; Tuberous sclerosis syndrome no assertion provided curation
Genetic Services Laboratory, University of Chicago RCV000118693 SCV000153108 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.

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