ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.3086G>T (p.Ser1029Ile)

dbSNP: rs796053450
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189858 SCV000243511 uncertain significance not provided 2014-11-20 criteria provided, single submitter clinical testing p.Ser1029Ile (AGT>ATT): c.3086 G>T in exon 23 of the TSC1 gene (NM_000368.4). The S1029I variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1029I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Additionally, the vast majority of TSC1 mutations result in protein truncation, while missense mutations have been reported only rarely (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether S1029I is a pathogenic mutation or a rare benign variant. The variant is found in TUBSC-EPIV2,TSC1 panel(s).
Invitae RCV000557141 SCV000641622 likely benign Tuberous sclerosis 1 2023-12-22 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000557141 SCV002040195 uncertain significance Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000557141 SCV003928130 uncertain significance Tuberous sclerosis 1 2023-04-27 criteria provided, single submitter clinical testing The TSC1 c.3086G>T (p.Ser1029Ile) missense change has a maximum subpopulation frequency of 0.0009% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. 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.
Ambry Genetics RCV004678635 SCV005174517 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-26 criteria provided, single submitter clinical testing The p.S1029I variant (also known as c.3086G>T), located in coding exon 21 of the TSC1 gene, results from a G to T substitution at nucleotide position 3086. The serine at codon 1029 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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