ClinVar Miner

Submissions for variant NM_014908.3(DOLK):c.1394G>A (p.Arg465His) (rs148930043)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213903 SCV000270157 likely benign not specified 2015-03-12 criteria provided, single submitter clinical testing p.Arg465His in exon 1 of DOLK: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, more than 10 mammals have a histidine (His) at this position despite high ne arby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. This variant has also been identified in 0.1% (7/10396) of African chromosomes by the Exome Aggregation Con sortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148930043).
Invitae RCV000639762 SCV000761343 uncertain significance Congenital disorder of glycosylation type 1M 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 465 of the DOLK protein (p.Arg465His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs148930043, ExAC 0.07%). This variant has not been reported in the literature in individuals with DOLK-related disease. ClinVar contains an entry for this variant (Variation ID: 227334). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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.

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