ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2144A>C (p.Glu715Ala)

gnomAD frequency: 0.00001  dbSNP: rs763351805
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070107 SCV001235319 uncertain significance Tuberous sclerosis 2 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 715 of the TSC2 protein (p.Glu715Ala). 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: 863196). 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 RCV002429741 SCV002726660 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-05 criteria provided, single submitter clinical testing The p.E715A variant (also known as c.2144A>C), located in coding exon 19 of the TSC2 gene, results from an A to C substitution at nucleotide position 2144. The glutamic acid at codon 715 is replaced by alanine, an amino acid with dissimilar 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.
Baylor Genetics RCV003462614 SCV004206900 uncertain significance Isolated focal cortical dysplasia type II 2023-06-19 criteria provided, single submitter clinical testing

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