Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000560278 | SCV000638507 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 442 of the DOLK protein (p.Ala442Thr). This variant is present in population databases (rs143641133, gnomAD 0.03%). 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: 464196). 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: "Benign"; 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. |
| Laboratory for Molecular Medicine, |
RCV000606924 | SCV000711611 | uncertain significance | not specified | 2017-01-30 | criteria provided, single submitter | clinical testing | The p.Ala442Thr variant in DOLK has not been previously reported in individuals with cardiomyopathy, but has been identified in 24/66724 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s143641133). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Ala442Thr variant is uncertain. |
| Ambry Genetics | RCV002384121 | SCV002692980 | uncertain significance | Cardiovascular phenotype | 2023-11-02 | criteria provided, single submitter | clinical testing | The p.A442T variant (also known as c.1324G>A), located in coding exon 1 of the DOLK gene, results from a G to A substitution at nucleotide position 1324. The alanine at codon 442 is replaced by threonine, an amino acid with similar properties. This variant was reported in a sudden infant death case with limited clinical information provided (Neubauer J et al. Eur. J. Hum. Genet., 2017 04;25:404-409). This amino acid position is well conserved in available 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, |
RCV000560278 | SCV002775888 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-10-05 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV005051794 | SCV005685413 | uncertain significance | Hypertrophic cardiomyopathy 26 | 2024-11-19 | criteria provided, single submitter | clinical testing | A DOLK c.1324G>A (p.Ala442Thr) variant was identified in a heterozygous state. This variant has been reported in the literature in an infant with sudden death (Neubauer J et al., PMID: 28074886). The DOLK c.1324G>A (p.Ala442Thr) variant has been reported in the ClinVar database as uncertain significance by four submitters (ClinVar variation ID: 464196) . Computational predictors suggest that the variant does not impact DOLK function. Due to limited information, the clinical significance of this DOLK c.1324G>A (p.Ala442Thr) variant is uncertain at this time. |