Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001305397 | SCV001494732 | uncertain significance | Tuberous sclerosis 2 | 2020-06-23 | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid 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. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 49672). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 544 of the TSC2 protein (p.Glu544Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Ambry Genetics | RCV002399401 | SCV002707613 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-03 | criteria provided, single submitter | clinical testing | The p.E544D variant (also known as c.1632G>T), located in coding exon 15 of the TSC2 gene, results from a G to T substitution at nucleotide position 1632. The glutamic acid at codon 544 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is 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. |
| Tuberous sclerosis database |
RCV000042934 | SCV000066731 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |