Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000223190 | SCV000277067 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-20 | criteria provided, single submitter | clinical testing | The p.R349W variant (also known as c.1045C>T), located in coding exon 9 of the MRE11A gene, results from a C to T substitution at nucleotide position 1045. The arginine at codon 349 is replaced by tryptophan, an amino acid with dissimilar 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, |
RCV000763777 | SCV000894679 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001064569 | SCV001229479 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 349 of the MRE11 protein (p.Arg349Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 29752822). ClinVar contains an entry for this variant (Variation ID: 232825). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV000763777 | SCV001481269 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2018-12-21 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |