ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1589T>C (p.Ile530Thr)

dbSNP: rs2151191974
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002022327 SCV002272548 uncertain significance Tuberous sclerosis 2 2025-01-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 530 of the TSC2 protein (p.Ile530Thr). 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: 1481581). 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.
Baylor Genetics RCV003464354 SCV004206887 uncertain significance Isolated focal cortical dysplasia type II 2023-07-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003886543 SCV004703057 uncertain significance not provided 2024-01-01 criteria provided, single submitter clinical testing TSC2: PM2
All of Us Research Program, National Institutes of Health RCV004011049 SCV004829106 uncertain significance Tuberous sclerosis syndrome 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 530 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 TSC2-related disorders 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.
Ambry Genetics RCV004042457 SCV005036324 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-23 criteria provided, single submitter clinical testing The p.I530T variant (also known as c.1589T>C), located in coding exon 14 of the TSC2 gene, results from a T to C substitution at nucleotide position 1589. The isoleucine at codon 530 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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