ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3899T>A (p.Met1300Lys)

gnomAD frequency: 0.00001  dbSNP: rs1349341137
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001223462 SCV001395614 uncertain significance Tuberous sclerosis 2 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1300 of the TSC2 protein (p.Met1300Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 951522). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TSC2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002366007 SCV002623625 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-16 criteria provided, single submitter clinical testing The p.M1300K variant (also known as c.3899T>A), located in coding exon 32 of the TSC2 gene, results from a T to A substitution at nucleotide position 3899. The methionine at codon 1300 is replaced by lysine, an amino acid with similar properties. 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.
All of Us Research Program, National Institutes of Health RCV004004797 SCV004837515 uncertain significance Tuberous sclerosis syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces methionine with lysine at codon 1300 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant 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.