ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.323A>G (p.Glu108Gly)

gnomAD frequency: 0.00006  dbSNP: rs779008975
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000614948 SCV000712576 uncertain significance not specified 2016-10-25 criteria provided, single submitter clinical testing The p.Glu108Gly variant in DOLK has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/11556 Latino and 3/66278 Europ ean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs779008975). Computational prediction tools and conservation a nalysis suggest that the p.Glu108Gly variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, th e clinical significance of the p.Glu108Gly variant is uncertain.
Invitae RCV001215223 SCV001386953 uncertain significance DK1-congenital disorder of glycosylation 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 108 of the DOLK protein (p.Glu108Gly). This variant is present in population databases (rs779008975, 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: 505389). 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: "Deleterious"; PolyPhen-2: "Probably 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.
GeneDx RCV001584420 SCV001817990 uncertain significance not provided 2023-06-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002325140 SCV002610331 uncertain significance Cardiovascular phenotype 2023-08-13 criteria provided, single submitter clinical testing The p.E108G variant (also known as c.323A>G), located in coding exon 1 of the DOLK gene, results from an A to G substitution at nucleotide position 323. The glutamic acid at codon 108 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001215223 SCV002794406 uncertain significance DK1-congenital disorder of glycosylation 2021-09-08 criteria provided, single submitter clinical testing

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