ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.646G>A (p.Glu216Lys)

gnomAD frequency: 0.00001  dbSNP: rs45517118
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644252 SCV000765944 likely benign Tuberous sclerosis 2 2024-08-01 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000042639 SCV000890989 uncertain significance Tuberous sclerosis syndrome 2021-08-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000644252 SCV002040560 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002354224 SCV002654749 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-27 criteria provided, single submitter clinical testing The p.E216K variant (also known as c.646G>A), located in coding exon 6 of the TSC2 gene, results from a G to A substitution at nucleotide position 646. The glutamic acid at codon 216 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. Functional analysis of this variant showed results comparable to wild type TSC2 (Hoogeveen-Westerveld M et al. Hum. Mutat., 2011 Apr;32:424-35). 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.
Fulgent Genetics, Fulgent Genetics RCV002490591 SCV002776190 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2021-12-27 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000644252 SCV003821609 uncertain significance Tuberous sclerosis 2 2023-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466894 SCV004206833 uncertain significance Isolated focal cortical dysplasia type II 2023-09-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000042639 SCV004836855 uncertain significance Tuberous sclerosis syndrome 2023-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998137 SCV005622740 uncertain significance not provided 2024-10-07 criteria provided, single submitter clinical testing The TSC2 c.646G>A (p.Glu216Lys) variant has not been reported in individuals with TSC2-related conditions in the published literature. A functional study characterized this variant as being probably neutral (PMID: 21309039 (2011)). The frequency of this variant in the general population, 0.000032 (1/31398 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Tuberous sclerosis database (TSC2) RCV000042639 SCV000066434 not provided Tuberous sclerosis syndrome no assertion provided curation

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