ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1988T>G (p.Leu663Arg)

dbSNP: rs1555506026
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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 RCV000644135 SCV000765825 uncertain significance Tuberous sclerosis 2 2024-06-30 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 663 of the TSC2 protein (p.Leu663Arg). 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: 535908). 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 RCV001013922 SCV001174566 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing The p.L663R variant (also known as c.1988T>G), located in coding exon 18 of the TSC2 gene, results from a T to G substitution at nucleotide position 1988. The leucine at codon 663 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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.
Genome-Nilou Lab RCV000644135 SCV002040660 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568428 SCV005054447 uncertain significance Isolated focal cortical dysplasia type II 2024-03-11 criteria provided, single submitter clinical testing

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