Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213646 | SCV000276512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | The p.H1269Y variant (also known as c.3805C>T), located in coding exon 25 of the RAD50 gene, results from a C to T substitution at nucleotide position 3805. The histidine at codon 1269 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000213646 | SCV000753299 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-03 | criteria provided, single submitter | clinical testing | 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 expected to disrupt RAD50 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 232384). 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 histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1269 of the RAD50 protein (p.His1269Tyr). |
Sema4, |
RCV002257523 | SCV002538518 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2021-09-02 | criteria provided, single submitter | curation |