ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.876C>G (p.Phe292Leu)

gnomAD frequency: 0.00005  dbSNP: rs147342916
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001309863 SCV001499376 uncertain significance DK1-congenital disorder of glycosylation 2022-06-20 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 292 of the DOLK protein (p.Phe292Leu). This variant is present in population databases (rs147342916, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1011976). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV002375391 SCV002685890 uncertain significance Cardiovascular phenotype 2023-04-08 criteria provided, single submitter clinical testing The p.F292L variant (also known as c.876C>G), located in coding exon 1 of the DOLK gene, results from a C to G substitution at nucleotide position 876. The phenylalanine at codon 292 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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.
Fulgent Genetics, Fulgent Genetics RCV001309863 SCV002776773 uncertain significance DK1-congenital disorder of glycosylation 2021-07-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001309863 SCV003832235 uncertain significance DK1-congenital disorder of glycosylation 2019-01-25 criteria provided, single submitter clinical testing
GeneDx RCV004727121 SCV005332731 uncertain significance not provided 2023-10-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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