ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3839C>G (p.Ser1280Cys)

gnomAD frequency: 0.00001  dbSNP: rs747522239
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165271 SCV000215988 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-16 criteria provided, single submitter clinical testing The p.S1280C variant (also known as c.3839C>G), located in coding exon 25 of the RAD50 gene, results from a C to G substitution at nucleotide position 3839. The serine at codon 1280 is replaced by cysteine, an amino acid with dissimilar 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 (formerly Invitae), Labcorp RCV000165271 SCV000628293 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1280 of the RAD50 protein (p.Ser1280Cys). This variant is present in population databases (rs747522239, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 185783). 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 with a positive predictive value of 80%. 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.
Sema4, Sema4 RCV002257467 SCV002538519 uncertain significance Nijmegen breakage syndrome-like disorder 2021-04-29 criteria provided, single submitter curation

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