ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4861A>G (p.Ile1621Val)

dbSNP: rs1555516628
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001023167 SCV001184999 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-03 criteria provided, single submitter clinical testing The p.I1621V variant (also known as c.4861A>G), located in coding exon 37 of the TSC2 gene, results from an A to G substitution at nucleotide position 4861. The isoleucine at codon 1621 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001067636 SCV001232705 uncertain significance Tuberous sclerosis 2 2023-06-28 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 825240). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1621 of the TSC2 protein (p.Ile1621Val).
GeneDx RCV001578205 SCV001805749 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant
Genome-Nilou Lab RCV001067636 SCV002040858 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003467673 SCV004206845 uncertain significance Isolated focal cortical dysplasia type II 2023-09-13 criteria provided, single submitter clinical testing

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