ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4102G>A (p.Gly1368Ser)

dbSNP: rs1596415966
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822829 SCV000963646 uncertain significance Tuberous sclerosis 2 2018-08-08 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC2-related disease. This sequence change replaces glycine with serine at codon 1368 of the TSC2 protein (p.Gly1368Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Ambry Genetics RCV002319920 SCV002626892 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-05 criteria provided, single submitter clinical testing The p.G1368S variant (also known as c.4102G>A), located in coding exon 33 of the TSC2 gene, results from a G to A substitution at nucleotide position 4102. The glycine at codon 1368 is replaced by serine, 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 RCV004002846 SCV004817861 uncertain significance Tuberous sclerosis syndrome 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 1368 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 tuberous sclerosis complex 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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