Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000163829 | SCV000214415 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.1222dupA pathogenic mutation, located in coding exon 10 of the MRE11A gene, results from a duplication of A at nucleotide position 1222, causing a translational frameshift with a predicted alternate stop codon (p.T408Nfs*49). This variant was reported in 1/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant was also identified in 1/692 men with metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis (Pritchard CC et al. N Engl J Med, 2016 Aug;375:443-53), as well as in a proband with pancreatic cancer (Hu C et al. JAMA 2018 06;319(23):2401-2409). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Ce |
RCV000761797 | SCV000891994 | likely pathogenic | not provided | 2019-05-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001052500 | SCV001216712 | pathogenic | Ataxia-telangiectasia-like disorder | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr408Asnfs*49) in the MRE11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). This variant is present in population databases (rs774440500, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). ClinVar contains an entry for this variant (Variation ID: 184556). For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV003444061 | SCV004171142 | likely pathogenic | Ataxia-telangiectasia-like disorder 1 | criteria provided, single submitter | not provided |