Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131699 | SCV000186736 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | The p.Q445R variant (also known as c.1334A>G), located in coding exon 12 of the MRE11A gene, results from an A to G substitution at nucleotide position 1334. The glutamine at codon 445 is replaced by arginine, an amino acid with highly 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. |
Fulgent Genetics, |
RCV000765027 | SCV000896216 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000992324 | SCV001144537 | uncertain significance | not provided | 2019-03-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002228505 | SCV002509596 | uncertain significance | Ataxia-telangiectasia-like disorder | 2023-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 445 of the MRE11 protein (p.Gln445Arg). This variant is present in population databases (rs371730091, gnomAD 0.04%). 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: 142523). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Baylor Genetics | RCV000765027 | SCV004193837 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2023-06-28 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000992324 | SCV004220913 | uncertain significance | not provided | 2019-03-28 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.00036 (9/24970 chromosomes in African/African-American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. In a large scale breast cancer association study, the variant was observed in a control individual and not among the breast cancer cases (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/MRE11A)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is disease causing or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |