Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702147 | SCV000830985 | uncertain significance | Tuberous sclerosis 2 | 2023-06-24 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs757347786, gnomAD 0.02%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 578982). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 740 of the TSC2 protein (p.Met740Thr). |
Sema4, |
RCV002255515 | SCV002531041 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-29 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002255515 | SCV002724827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-12 | criteria provided, single submitter | clinical testing | The p.M740T variant (also known as c.2219T>C), located in coding exon 19 of the TSC2 gene, results from a T to C substitution at nucleotide position 2219. The methionine at codon 740 is replaced by threonine, an amino acid with 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. |
Gene |
RCV003442046 | SCV004169865 | uncertain significance | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |