ClinVar Miner

Submissions for variant NM_033068.3(ACP4):c.746C>T (p.Pro249Leu) (rs1085307111)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Leeds Amelogenesis Imperfecta Research Group, University of Leeds RCV000489871 SCV000494662 pathogenic Amelogenesis imperfecta, type IJ 2016-10-28 no assertion criteria provided research The variant is predicted to be pathogenic / deleterious by a number of different algorithms, including polyphen-2, CADD, and SIFT. The affected residue P249 (NP_149059.1) is conserved in mammalian orthologues but not in paralogous sequences. The residue lies within in the extracellular domain (residues 29-390) of ACPT. P249 is predicted to form a twist between two alpha helices (Swissmodel Q9BZG2), and substitution of a rigid proline at position 249 with the much larger leucine (BLOSUM62 score -3) is likely to influence the structure of the active site by disrupting that twist.The variant is absent from publicly available databases of variation including dbSNP146, Exome Variant Server and ExAC v0.3.

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