Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556710 | SCV000628220 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 457418). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 915 of the RAD50 protein (p.Leu915Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV000556710 | SCV000663640 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-09-26 | criteria provided, single submitter | clinical testing | The p.L915F variant (also known as c.2745G>C), located in coding exon 17 of the RAD50 gene, results from a G to C substitution at nucleotide position 2745. The leucine at codon 915 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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. |