ClinVar Miner

Submissions for variant NM_014908.3(DOLK):c.931G>T (p.Ala311Ser) (rs1554826773)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519803 SCV000619030 uncertain significance not provided 2017-07-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DOLK gene. The A311S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A311S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, additional evidence is needed to determine whether this variant is pathogenic or benign.
Invitae RCV000703948 SCV000832878 uncertain significance Congenital disorder of glycosylation type 1M 2018-04-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 311 of the DOLK protein (p.Ala311Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DOLK-related disease. ClinVar contains an entry for this variant (Variation ID: 450442). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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.

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