ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.1431G>A (p.Met477Ile)

gnomAD frequency: 0.00005  dbSNP: rs754150966
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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 RCV001327240 SCV001518305 uncertain significance DK1-congenital disorder of glycosylation 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 477 of the DOLK protein (p.Met477Ile). This variant is present in population databases (rs754150966, 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: 1026749). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002395727 SCV002702800 uncertain significance Cardiovascular phenotype 2023-05-31 criteria provided, single submitter clinical testing The p.M477I variant (also known as c.1431G>A), located in coding exon 1 of the DOLK gene, results from a G to A substitution at nucleotide position 1431. The methionine at codon 477 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not 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, Fulgent Genetics RCV001327240 SCV002775528 uncertain significance DK1-congenital disorder of glycosylation 2021-08-30 criteria provided, single submitter clinical testing

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