ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4192C>G (p.Leu1398Val)

gnomAD frequency: 0.00001  dbSNP: rs1060500928
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459017 SCV000544372 uncertain significance Tuberous sclerosis 2 2022-07-23 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1398 of the TSC2 protein (p.Leu1398Val). 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: 405993). 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. 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.
GeneDx RCV000522580 SCV000620377 uncertain significance not provided 2022-07-29 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
Ambry Genetics RCV000561438 SCV000675698 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-08 criteria provided, single submitter clinical testing The p.L1398V variant (also known as c.4192C>G), located in coding exon 33 of the TSC2 gene, results from a C to G substitution at nucleotide position 4192. The leucine at codon 1398 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well 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.
Genome-Nilou Lab RCV000459017 SCV002040810 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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