ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.34G>A (p.Val12Met)

gnomAD frequency: 0.00001  dbSNP: rs755022536
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542137 SCV000628270 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 12 of the RAD50 protein (p.Val12Met). This variant is present in population databases (rs755022536, gnomAD 0.006%). 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: 457454). 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.
Ambry Genetics RCV000542137 SCV000671772 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing The p.V12M variant (also known as c.34G>A), located in coding exon 1 of the RAD50 gene, results from a G to A substitution at nucleotide position 34. The valine at codon 12 is replaced by methionine, an amino acid with highly similar 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.
Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital RCV003313092 SCV004012935 uncertain significance Neuroepithelial tumor, PATZ1 fusion-positive 2021-04-22 criteria provided, single submitter research

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