ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2653A>G (p.Ile885Val)

dbSNP: rs1555508581
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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 RCV000644070 SCV000765760 uncertain significance Tuberous sclerosis 2 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 885 of the TSC2 protein (p.Ile885Val). 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: 535859). 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 RCV003343971 SCV004057695 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-03 criteria provided, single submitter clinical testing The p.I885V variant (also known as c.2653A>G), located in coding exon 23 of the TSC2 gene, results from an A to G substitution at nucleotide position 2653. The isoleucine at codon 885 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx RCV004773063 SCV005384928 uncertain significance not provided 2024-02-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 38137511)
All of Us Research Program, National Institutes of Health RCV004802327 SCV005427152 uncertain significance Tuberous sclerosis syndrome 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 885 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. 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.

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