Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000691766 | SCV000819557 | uncertain significance | Tuberous sclerosis 2 | 2023-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 740 of the TSC2 protein (p.Met740Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 570811). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV002424627 | SCV002728798 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-30 | criteria provided, single submitter | clinical testing | The p.M740V variant (also known as c.2218A>G), located in coding exon 19 of the TSC2 gene, results from an A to G substitution at nucleotide position 2218. The methionine at codon 740 is replaced by valine, an amino acid with highly similar 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. |
Fulgent Genetics, |
RCV002485648 | SCV002785762 | uncertain significance | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2022-01-13 | criteria provided, single submitter | clinical testing | |
Gharavi Laboratory, |
RCV000722723 | SCV000853854 | uncertain significance | not provided | 2018-09-16 | no assertion criteria provided | research |