ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.859G>A (p.Glu287Lys)

dbSNP: rs397515300
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687612 SCV000815189 uncertain significance Tuberous sclerosis 2 2023-05-07 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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 287 of the TSC2 protein (p.Glu287Lys). 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: 567506). 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.
Ambry Genetics RCV003163116 SCV003863354 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-27 criteria provided, single submitter clinical testing The p.E287K variant (also known as c.859G>A), located in coding exon 9 of the TSC2 gene, results from a G to A substitution at nucleotide position 859. The glutamic acid at codon 287 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV004802357 SCV005427054 uncertain significance Tuberous sclerosis syndrome 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 287 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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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