Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000216532 | SCV000278130 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-21 | criteria provided, single submitter | clinical testing | The p.M618R variant (also known as c.1853T>G), located in coding exon 15 of the MRE11A gene, results from a T to G substitution at nucleotide position 1853. The methionine at codon 618 is replaced by arginine, an amino acid with similar properties. This amino acid position is highly 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. |
| Illumina Laboratory Services, |
RCV000330635 | SCV000374925 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV001324948 | SCV001515919 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-05-14 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 618 of the MRE11 protein (p.Met618Arg). This variant is present in population databases (rs748933763, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 233699). 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. |