Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000560978 | SCV000671781 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-11 | criteria provided, single submitter | clinical testing | The p.I429M variant (also known as c.1287A>G), located in coding exon 9 of the RAD50 gene, results from an A to G substitution at nucleotide position 1287. The isoleucine at codon 429 is replaced by methionine, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000560978 | SCV000753306 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 484649). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 429 of the RAD50 protein (p.Ile429Met). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264575 | SCV001442798 | uncertain significance | not specified | 2020-10-09 | criteria provided, single submitter | clinical testing | Variant summary: RAD50 c.1287A>G (p.Ile429Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248772 control chromosomes. 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.1287A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV003459368 | SCV004207331 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-09-26 | criteria provided, single submitter | clinical testing |