ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3865A>G (p.Arg1289Gly)

dbSNP: rs2090265922
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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 RCV001060616 SCV001225317 uncertain significance Tuberous sclerosis 2 2024-07-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1289 of the TSC2 protein (p.Arg1289Gly). 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: 855361). 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 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 RCV002355063 SCV002620004 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-20 criteria provided, single submitter clinical testing The p.R1289G variant (also known as c.3865A>G), located in coding exon 31 of the TSC2 gene, results from an A to G substitution at nucleotide position 3865. The arginine at codon 1289 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 RCV004000116 SCV004834914 uncertain significance Tuberous sclerosis syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 1289 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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.
Baylor Genetics RCV004570245 SCV005054489 uncertain significance Isolated focal cortical dysplasia type II 2023-12-21 criteria provided, single submitter clinical testing

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