ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2359G>A (p.Glu787Lys)

dbSNP: rs45517231
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803364 SCV000943230 uncertain significance Tuberous sclerosis 2 2023-05-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 787 of the TSC2 protein (p.Glu787Lys). 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. 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. ClinVar contains an entry for this variant (Variation ID: 648606). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency).
GeneDx RCV001585730 SCV001810678 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek 2016)
Genome-Nilou Lab RCV000803364 SCV002040696 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002442675 SCV002733168 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-17 criteria provided, single submitter clinical testing The p.E787K variant (also known as c.2359G>A), located in coding exon 21 of the TSC2 gene, results from a G to A substitution at nucleotide position 2359. The glutamic acid at codon 787 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.

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