Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566485 | SCV000669134 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-25 | criteria provided, single submitter | clinical testing | The p.I117V variant (also known as c.349A>G), located in coding exon 2 of the CDK4 gene, results from an A to G substitution at nucleotide position 349. The isoleucine at codon 117 is replaced by valine, an amino acid with highly similar properties. This variant has been reported in an individual affected with colorectal cancer (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). 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. |
| Invitae | RCV001053516 | SCV001217783 | uncertain significance | Familial melanoma | 2023-09-17 | 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 117 of the CDK4 protein (p.Ile117Val). This variant is present in population databases (rs776343973, gnomAD 0.002%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 483303). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |