ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.589G>A (p.Val197Ile)

gnomAD frequency: 0.00002  dbSNP: rs373587710
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001367584 SCV001563938 uncertain significance DK1-congenital disorder of glycosylation 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 197 of the DOLK protein (p.Val197Ile). This variant is present in population databases (rs373587710, gnomAD 0.02%). 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: 1058442). 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 with a negative predictive value of 80%. 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 RCV002357248 SCV002653179 uncertain significance Cardiovascular phenotype 2022-10-07 criteria provided, single submitter clinical testing The p.V197I variant (also known as c.589G>A), located in coding exon 1 of the DOLK gene, results from a G to A substitution at nucleotide position 589. The valine at codon 197 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine 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 RCV001367584 SCV002797067 uncertain significance DK1-congenital disorder of glycosylation 2021-11-17 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004692650 SCV005191125 uncertain significance not provided criteria provided, single submitter not provided

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