Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001211267 | SCV001382797 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2021-09-24 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 300 of the MEN1 protein (p.Thr300Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Ambry Genetics | RCV002375161 | SCV002683726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-03 | criteria provided, single submitter | clinical testing | The p.T300I variant (also known as c.899C>T), located in coding exon 5 of the MEN1 gene, results from a C to T substitution at nucleotide position 899. The threonine at codon 300 is replaced by isoleucine, an amino acid with 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. |
Laboratory of Medical Genetics Unit, |
RCV003314679 | SCV004012975 | uncertain significance | Diffuse midline glioma, H3 K27-altered | 2021-03-04 | criteria provided, single submitter | research |