Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131613 | SCV000186629 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.I620V variant (also known as c.1858A>G), located in coding exon 15 of the MRE11A gene, results from an A to G substitution at nucleotide position 1858. The isoleucine at codon 620 is replaced by valine, an amino acid with highly similar properties. This variant was reported in 14/60,466 breast cancer cases and in 9/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is highly 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. |
Illumina Laboratory Services, |
RCV000263891 | SCV000374924 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001065906 | SCV001230896 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 620 of the MRE11 protein (p.Ile620Val). This variant is present in population databases (rs144070976, gnomAD 0.007%). 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: 142478). 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. |
Fulgent Genetics, |
RCV000263891 | SCV002789817 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2022-04-16 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003422026 | SCV004117320 | uncertain significance | MRE11-related condition | 2022-10-19 | criteria provided, single submitter | clinical testing | The MRE11 c.1858A>G variant is predicted to result in the amino acid substitution p.Ile620Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0071% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-94178985-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |