ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1317C>A (p.Asp439Glu)

dbSNP: rs777457815
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539682 SCV000644228 uncertain significance Tuberous sclerosis 2 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 439 of the TSC2 protein (p.Asp439Glu). This variant is not present in population databases (gnomAD no frequency). 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: 467860). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. 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 RCV000562035 SCV000675678 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-26 criteria provided, single submitter clinical testing The p.D439E variant (also known as c.1317C>A), located in coding exon 12 of the TSC2 gene, results from a C to A substitution at nucleotide position 1317. The aspartic acid at codon 439 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is 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.
Genome-Nilou Lab RCV000539682 SCV002040602 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV003236813 SCV003935680 uncertain significance not provided 2023-06-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003459238 SCV004206876 uncertain significance Isolated focal cortical dysplasia type II 2023-07-27 criteria provided, single submitter clinical testing

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.