Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213127 | SCV000278613 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-15 | criteria provided, single submitter | clinical testing | The p.T329S variant (also known as c.986C>G), located in coding exon 8 of the MRE11A gene, results from a C to G substitution at nucleotide position 986. The threonine at codon 329 is replaced by serine, an amino acid with 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. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781548 | SCV000919681 | uncertain significance | not specified | 2018-10-08 | criteria provided, single submitter | clinical testing | Variant summary: MRE11A c.986C>G (p.Thr329Ser) results in a conservative amino acid change located in the Mre11, DNA-binding domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 245906 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.986C>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001057384 | SCV001221873 | uncertain significance | Ataxia-telangiectasia-like disorder | 2025-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 329 of the MRE11 protein (p.Thr329Ser). This variant is present in population databases (rs370645480, gnomAD 0.006%). 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: 234106). 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. |
| Fulgent Genetics, |
RCV005008172 | SCV005631444 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2024-04-30 | criteria provided, single submitter | clinical testing |