ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2227G>A (p.Gly743Ser)

dbSNP: rs1555506852
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541585 SCV000644331 uncertain significance Tuberous sclerosis 2 2022-11-08 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 467931). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 743 of the TSC2 protein (p.Gly743Ser).
Ambry Genetics RCV003380613 SCV004098257 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-11 criteria provided, single submitter clinical testing The p.G743S variant (also known as c.2227G>A), located in coding exon 20 of the TSC2 gene, results from a G to A substitution at nucleotide position 2227. The glycine at codon 743 is replaced by serine, an amino acid with 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.

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