ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.850C>T (p.Arg284Cys)

gnomAD frequency: 0.00003  dbSNP: rs140544652
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000231351 SCV000284742 benign Tuberous sclerosis 1 2025-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017933 SCV001179100 likely benign Hereditary cancer-predisposing syndrome 2021-09-02 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.
GeneDx RCV001575957 SCV001803052 likely benign not provided 2021-07-23 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000231351 SCV002040143 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001017933 SCV002531491 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-07 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV003407768 SCV004109481 uncertain significance TSC1-related disorder 2023-03-10 criteria provided, single submitter clinical testing The TSC1 c.850C>T variant is predicted to result in the amino acid substitution p.Arg284Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-135787732-G-A). This variant is listed with conflicting interpretations of uncertain, likely benign and benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/237729/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000231351 SCV005689347 uncertain significance Tuberous sclerosis 1 2025-02-05 criteria provided, single submitter clinical testing The TSC1 c.850C>T (p.Arg284Cys) missense change has a maximum subpopulation frequency of 0.008% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.