Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000494325 | SCV000581935 | uncertain significance | not provided | 2017-05-05 | criteria provided, single submitter | clinical testing | The P287L variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. This substitution occurs at a position that is conserved across species and is located within the regions reported to interact with Set1-like complex and bind to hPAf1 complex, RNAPII, and PAF1 (Rozanblatt-Rosen et al., 2005; Yart et al., 2005). In silico analyses predict that this variant is probably damaging to protein structure and function. We interpret P287L as a variant of uncertain significance. |
Labcorp Genetics |
RCV003607295 | SCV004504249 | uncertain significance | Parathyroid carcinoma | 2023-05-20 | 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 not expected to disrupt CDC73 protein function. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 287 of the CDC73 protein (p.Pro287Leu). This variant is not present in population databases (gnomAD no frequency). 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: 429379). 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. |