ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.385G>A (p.Asp129Asn) (rs876660606)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220682 SCV000278171 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-07 criteria provided, single submitter clinical testing The p.D129N variant (also known as c.385G>A), located in coding exon 3 of the CDK4 gene, results from a G to A substitution at nucleotide position 385. The aspartic acid at codon 129 is replaced by asparagine, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589773 SCV000695316 uncertain significance not provided 2016-05-27 criteria provided, single submitter clinical testing Variant summary: The CDK4 c.385G>A (p.Asp129Asn) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was absent in 121406 control chromosomes and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000805185 SCV000945132 uncertain significance Hereditary melanoma 2020-04-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 129 of the CDK4 protein (p.Asp129Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 233735). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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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