ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3358G>C (p.Val1120Leu)

dbSNP: rs1053311636
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527776 SCV000644427 benign Tuberous sclerosis 2 2024-01-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569864 SCV000675563 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-13 criteria provided, single submitter clinical testing The p.V1120L variant (also known as c.3358G>C), located in coding exon 28 of the TSC2 gene, results from a G to C substitution at nucleotide position 3358. The valine at codon 1120 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001584294 SCV001819025 likely benign not provided 2019-09-13 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function Has not been previously published as pathogenic or benign to our knowledge
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001584294 SCV002011335 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000527776 SCV002039736 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003419961 SCV004108866 uncertain significance TSC2-related condition 2022-10-20 criteria provided, single submitter clinical testing The TSC2 c.3358G>C variant is predicted to result in the amino acid substitution p.Val1120Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 1 out of ~239,548 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/16-2129631-G-C) and has conflicting interpretations ranging from benign to uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/468005/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Clinical Genomics Laboratory, Washington University in St. Louis RCV000527776 SCV004177169 uncertain significance Tuberous sclerosis 2 2023-08-11 criteria provided, single submitter clinical testing The TSC2 c.3358G>C (p.Val1120Leu) variant was identified at a near heterozygous allelic fraction. This variant has been reported in the ClinVar database as benign/likely benign/variant of uncertain significance by five submitters (ClinVar Variation ID: 468005). The TSC2 c.3358G>C (p.Val1120Leu) variant is rarely observed (1/152240 alleles) in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are conflicting as to the impact of this variant on the TSC2 function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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