Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214403 | SCV000278519 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-09-24 | criteria provided, single submitter | clinical testing | The p.T879S variant (also known as c.2636C>G), located in coding exon 16 of the RAD50 gene, results from a C to G substitution at nucleotide position 2636. The threonine at codon 879 is replaced by serine, an amino acid with 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort.This amino acid position is not well conserved however, serine is a reference amino acid in several species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence for this variant is limited at this time, the clinical significance of p.T879S remains unclear. |
Invitae | RCV000214403 | SCV001216197 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | 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: 234034). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 879 of the RAD50 protein (p.Thr879Ser). |
Baylor Genetics | RCV003463598 | SCV004207389 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-06-21 | criteria provided, single submitter | clinical testing |