ClinVar Miner

Submissions for variant NM_014908.3(DOLK):c.1324G>A (p.Ala442Thr) (rs143641133)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000560278 SCV000638507 uncertain significance Congenital disorder of glycosylation type 1M 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 442 of the DOLK protein (p.Ala442Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs143641133, ExAC 0.04%). This variant has been reported in an infant with sudden infant death syndrome (PMID: 28074886). ClinVar contains an entry for this variant (Variation ID: 464196). 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: "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,Partners HealthCare Personalized 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.

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