Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000537208 | SCV000644365 | uncertain significance | Tuberous sclerosis 2 | 2023-09-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 467959). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 907 of the TSC2 protein (p.Asp907Tyr). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Ambry Genetics | RCV002431635 | SCV002741442 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-09 | criteria provided, single submitter | clinical testing | The p.D907Y variant (also known as c.2719G>T), located in coding exon 23 of the TSC2 gene, results from a G to T substitution at nucleotide position 2719. The aspartic acid at codon 907 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Gene |
RCV003228946 | SCV003925893 | uncertain significance | not provided | 2022-11-17 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |