Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131542 | SCV000186541 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.N413S variant (also known as c.1238A>G), located in coding exon 11 of the MRE11A gene, results from an A to G substitution at nucleotide position 1238. The asparagine at codon 413 is replaced by serine, an amino acid with highly similar properties. This alteration was reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J. Med. Genet. 2016 Jun;53:366-76). 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, |
RCV000376230 | SCV000374932 | uncertain significance | Ataxia-telangiectasia-like disorder 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV002228663 | SCV000547417 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 413 of the MRE11 protein (p.Asn413Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs587782457, ExAC 0.002%). 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: 142427). 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. |
| Athena Diagnostics Inc | RCV001289101 | SCV001476694 | uncertain significance | not provided | 2020-03-06 | criteria provided, single submitter | clinical testing |