Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001368801 | SCV001565214 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-10-25 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 220364). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 254 of the MRE11 protein (p.Thr254Ile). |
| Ambry Genetics | RCV000204960 | SCV002755912 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-22 | criteria provided, single submitter | clinical testing | The p.T254I variant (also known as c.761C>T), located in coding exon 7 of the MRE11A gene, results from a C to T substitution at nucleotide position 761. The threonine at codon 254 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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. |