Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002426588 | SCV002744711 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-14 | criteria provided, single submitter | clinical testing | The p.M895V variant (also known as c.2683A>G), located in coding exon 23 of the TSC2 gene, results from an A to G substitution at nucleotide position 2683. The methionine at codon 895 is replaced by valine, an amino acid with highly similar properties. In one study, this alteration was identified in 1/126 unrelated patients with a clinical diagnosis of Tuberous Sclerosis (Niida Y et al. Hum Mutat, 1999;14:412-22). This alteration was also identified in an individual with cortical dysplasias and epilepsy (Meng Y et al. J Hum Genet, 2021 Mar;66:227-236). 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. |
| Invitae | RCV002514175 | SCV003443038 | uncertain significance | Tuberous sclerosis 2 | 2022-02-22 | 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. 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: 50091). This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 10533067). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 895 of the TSC2 protein (p.Met895Val). |
| Tuberous sclerosis database |
RCV000043357 | SCV000067163 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |