Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130212 | SCV000185050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-28 | criteria provided, single submitter | clinical testing | The p.N931H variant (also known as c.2791A>C), located in coding exon 17 of the RAD50 gene, results from an A to C substitution at nucleotide position 2791. The asparagine at codon 931 is replaced by histidine, 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. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is not 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 p.N931H remains unclear. |
Invitae | RCV000130212 | SCV001403448 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-22 | 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: 141619). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 931 of the RAD50 protein (p.Asn931His). |