ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.862C>G (p.Arg288Gly)

dbSNP: rs587779897
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115329 SCV000149238 uncertain significance not provided 2014-02-05 criteria provided, single submitter clinical testing This variant is denoted CDK4 c.862C>G at the cDNA level, p.Arg288Gly (R288G) at the protein level, and results in the change of an Arginine to a Glycine (CGA>GGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDK4 Arg288Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a positive polar amino acid is replaced with a neutral non-polar one, altering a position that is moderately conserved throughout evolution and is located in the Protein kinase domain (UniProt). In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we consider CDK4 Arg288Gly to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854548 SCV002179215 uncertain significance Familial melanoma 2022-01-22 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CDK4-related conditions. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 288 of the CDK4 protein (p.Arg288Gly). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 127521). 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 CDK4 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.

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