Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004956317 | SCV005448869 | uncertain significance | Inborn genetic diseases | 2024-11-27 | criteria provided, single submitter | clinical testing | The p.V1133M variant (also known as c.3397G>A), located in coding exon 15 of the MECOM gene, results from a G to A substitution at nucleotide position 3397. The valine at codon 1133 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV005107482 | SCV005804947 | uncertain significance | not provided | 2024-06-02 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 945 of the MECOM protein (p.Val945Met). This variant is present in population databases (rs749026364, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MECOM-related conditions. 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 methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |