ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.1163G>A (p.Arg388Gln) (rs587780134)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212567 SCV000149812 uncertain significance not provided 2014-01-13 criteria provided, single submitter clinical testing MRE11A has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted MRE11A c.1163G>A at the cDNA level, p.Arg388Gln (R388Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MRE11A Arg388Gln 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. This variant is a semi-conservative substitution in which a positive polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the MRE11A gene, remain unclear.
Ambry Genetics RCV000115903 SCV000218230 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-06 criteria provided, single submitter clinical testing The p.R388Q variant (also known as c.1163G>A), located in coding exon 10 of the MRE11A gene, results from a G to A substitution at nucleotide position 1163. The arginine at codon 388 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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.
Invitae RCV000791404 SCV000261284 uncertain significance Ataxia-telangiectasia-like disorder 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 388 of the MRE11A protein (p.Arg388Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (ExAC 0.02%) but has not been reported in the literature. ClinVar contains an entry for this variant (Variation ID: 127969). 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, but these predictions have not been confirmed by published functional studies. However, algorithms developed to predict the effect of nucleotide substitutions on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has also not been confirmed by published transcriptional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765029 SCV000896218 uncertain significance Ataxia-telangiectasia-like disorder 1 2018-10-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000212567 SCV001476693 uncertain significance not provided 2019-10-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV000765029 SCV001483057 uncertain significance Ataxia-telangiectasia-like disorder 1 2019-04-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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