ClinVar Miner

Submissions for variant NM_024529.5(CDC73):c.754A>G (p.Ile252Val)

gnomAD frequency: 0.00001  dbSNP: rs374290883
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001222413 SCV001394511 uncertain significance Parathyroid carcinoma 2023-11-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 252 of the CDC73 protein (p.Ile252Val). This variant is present in population databases (rs374290883, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CDC73-related conditions. ClinVar contains an entry for this variant (Variation ID: 950658). 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 CDC73 protein function with a negative 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.
Ambry Genetics RCV002393539 SCV002670802 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-05 criteria provided, single submitter clinical testing The p.I252V variant (also known as c.754A>G), located in coding exon 8 of the CDC73 gene, results from an A to G substitution at nucleotide position 754. The isoleucine at codon 252 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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 this alteration remains unclear.
Baylor Genetics RCV003462756 SCV004215574 uncertain significance Hyperparathyroidism 1 2023-09-09 criteria provided, single submitter clinical testing

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