ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.64C>T (p.Arg22Trp)

gnomAD frequency: 0.00001  dbSNP: rs749030456
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
Ambry Genetics RCV000573120 SCV000664650 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-09 criteria provided, single submitter clinical testing The p.R22W variant (also known as c.64C>T), located in coding exon 1 of the TSC1 gene, results from a C to T substitution at nucleotide position 64. The arginine at codon 22 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with core binding factor acute myeloid leukemia (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). This variant was also identified in 1/190 unrelated Chinese patients under the age of 45 who presented with renal tumors (Wu J et al. Cancer, 2019 04;125:1060-1069). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001721544 SCV000715014 likely benign not provided 2020-06-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000695216 SCV000823701 likely benign Tuberous sclerosis 1 2025-02-02 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001526808 SCV001737445 uncertain significance Tuberous sclerosis syndrome 2021-05-20 criteria provided, single submitter clinical testing The TSC1 c.64C>T (p.Arg22Trp) missense change has a maximum frequency of 0.011% in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/17-17125860-G-T?dataset=gnomad_r2_1). In silico tools are not in agreement about the effect of this variant on protein function. Functional assays indicate that this variant may disrupt the TSC1-TSC2 complex and activate the mTOR pathway (PMID: 28215400). This variant was identified as a low-level somatic mutation in the brain tissue of three individuals with focal cortical dysplasia (PMID: 28215400). To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting.
Genome-Nilou Lab RCV000695216 SCV002040517 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000573120 SCV002531476 likely benign Hereditary cancer-predisposing syndrome 2021-04-30 criteria provided, single submitter curation
OMIM RCV000477710 SCV000564179 pathogenic Isolated focal cortical dysplasia type II 2017-04-11 no assertion criteria provided literature only

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.