Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214989 | SCV000278433 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-29 | criteria provided, single submitter | clinical testing | The p.S541I variant (also known as c.1622G>T), located in coding exon 14 of the MRE11A gene, results from a G to T substitution at nucleotide position 1622. The serine at codon 541 is replaced by isoleucine, an amino acid with dissimilar 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 | RCV001242278 | SCV001415352 | uncertain significance | Ataxia-telangiectasia-like disorder | 2023-01-19 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 233958). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 541 of the MRE11 protein (p.Ser541Ile). |