Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000217455 | SCV000277140 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-30 | criteria provided, single submitter | clinical testing | The p.L929S variant (also known as c.2786T>C), located in coding exon 17 of the RAD50 gene, results from a T to C substitution at nucleotide position 2786. The leucine at codon 929 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000217455 | SCV000628222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-19 | 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: 232884). 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 leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 929 of the RAD50 protein (p.Leu929Ser). |