ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.14G>A (p.Arg5Gln) (rs1031329993)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479385 SCV000567382 uncertain significance not provided 2017-07-05 criteria provided, single submitter clinical testing This variant is denoted CDK4 c.14G>A at the cDNA level, p.Arg5Gln (R5Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDK4 Arg5Gln was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. CDK4 Arg5Gln occurs at a position that is conserved in mammals and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether CDK4 Arg5Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562440 SCV000669142 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-07 criteria provided, single submitter clinical testing The p.R5Q variant (also known as c.14G>A), located in coding exon 1 of the CDK4 gene, results from a G to A substitution at nucleotide position 14. The arginine at codon 5 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well 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 RCV000793196 SCV000932537 uncertain significance Hereditary melanoma 2020-07-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 5 of the CDK4 protein (p.Arg5Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 419527). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001111713 SCV001269295 likely benign Cutaneous malignant melanoma 3 2017-08-09 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.