ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.434G>C (p.Gly145Ala)

gnomAD frequency: 0.00005  dbSNP: rs377064301
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Total submissions: 4
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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 RCV000612856 SCV000711612 uncertain significance not specified 2016-06-10 criteria provided, single submitter clinical testing The p.Gly145Ala variant in DOLK has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/10346 African chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3 77064301). Computational prediction tools and conservation analysis suggest that the p.Gly145Ala variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical signif icance of the p.Gly145Ala variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001057488 SCV001221985 uncertain significance DK1-congenital disorder of glycosylation 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 145 of the DOLK protein (p.Gly145Ala). This variant is present in population databases (rs377064301, 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: 504837). 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 DOLK 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 RCV002331032 SCV002632203 uncertain significance Cardiovascular phenotype 2021-10-11 criteria provided, single submitter clinical testing The p.G145A variant (also known as c.434G>C), located in coding exon 1 of the DOLK gene, results from a G to C substitution at nucleotide position 434. The glycine at codon 145 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001057488 SCV002779704 uncertain significance DK1-congenital disorder of glycosylation 2021-11-05 criteria provided, single submitter clinical testing

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