ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.463A>T (p.Met155Leu)

gnomAD frequency: 0.00001  dbSNP: rs1218829181
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001315587 SCV001506165 uncertain significance DK1-congenital disorder of glycosylation 2020-06-16 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with DOLK-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 155 of the DOLK protein (p.Met155Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine.
Ambry Genetics RCV002329268 SCV002633596 uncertain significance Cardiovascular phenotype 2021-05-09 criteria provided, single submitter clinical testing The p.M155L variant (also known as c.463A>T), located in coding exon 1 of the DOLK gene, results from an A to T substitution at nucleotide position 463. The methionine at codon 155 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine 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.

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