ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5134G>A (p.Ala1712Thr)

dbSNP: rs1596457926
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801997 SCV000941803 uncertain significance Tuberous sclerosis 2 2024-09-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1712 of the TSC2 protein (p.Ala1712Thr). 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: 647482). 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.
Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital RCV003325215 SCV004012941 uncertain significance Astroblastoma, MN1-altered 2022-03-30 criteria provided, single submitter research
Baylor Genetics RCV004569581 SCV005054488 uncertain significance Isolated focal cortical dysplasia type II 2023-12-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV004949933 SCV005527635 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-14 criteria provided, single submitter clinical testing The p.A1712T variant (also known as c.5134G>A), located in coding exon 39 of the TSC2 gene, results from a G to A substitution at nucleotide position 5134. The alanine at codon 1712 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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