ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.581C>T (p.Ala194Val)

gnomAD frequency: 0.00001  dbSNP: rs763132281
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001877798 SCV002139402 uncertain significance DK1-congenital disorder of glycosylation 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 194 of the DOLK protein (p.Ala194Val). This variant is present in population databases (rs763132281, gnomAD 0.002%). 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: 1374384). 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 RCV002359332 SCV002650776 uncertain significance Cardiovascular phenotype 2023-09-30 criteria provided, single submitter clinical testing The p.A194V variant (also known as c.581C>T), located in coding exon 1 of the DOLK gene, results from a C to T substitution at nucleotide position 581. The alanine at codon 194 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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 RCV001877798 SCV002783006 uncertain significance DK1-congenital disorder of glycosylation 2021-11-12 criteria provided, single submitter clinical testing

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