Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002010611 | SCV002295210 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2021-06-16 | 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 expected to disrupt MEN1 protein function. This variant has not been reported in the literature in individuals with MEN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 335 of the MEN1 protein (p.Arg335Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Ambry Genetics | RCV002398081 | SCV002706205 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-20 | criteria provided, single submitter | clinical testing | The p.R335G variant (also known as c.1003C>G), located in coding exon 6 of the MEN1 gene, results from a C to G substitution at nucleotide position 1003. The arginine at codon 335 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |