Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481354 | SCV000567016 | uncertain significance | not provided | 2015-06-24 | criteria provided, single submitter | clinical testing | This variant is denoted MUTYH c.662G>C at the cDNA level, p.Gly221Ala (G221A) at the protein level, and results in the change of a Glycine to an Alanine (GGG>GCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH Gly221Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glycine and Alanine share similar properties, this is considered a conservative amino acid substitution. MUTYH Gly221Ala occurs at a position that is conserved across species and is not located in a known functional domain (Ruggieri 2013, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MUTYH Gly221Ala is pathogenic or benign. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two pathogenic variants on opposite chromosomes in MUTYH. |
| Labcorp Genetics |
RCV000640382 | SCV000761973 | uncertain significance | Familial adenomatous polyposis 2 | 2021-03-24 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 419302). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 221 of the MUTYH protein (p.Gly221Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. |
| Ambry Genetics | RCV001025477 | SCV001187674 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | The p.G221A variant (also known as c.662G>C), located in coding exon 8 of the MUTYH gene, results from a G to C substitution at nucleotide position 662. The glycine at codon 221 is replaced by alanine, an amino acid with similar properties. This amino acid position is well 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. |
| All of Us Research Program, |
RCV000640382 | SCV004826982 | uncertain significance | Familial adenomatous polyposis 2 | 2023-04-27 | criteria provided, single submitter | clinical testing |