ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.3460C>T (p.Arg1154Trp) (rs387907208)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546897 SCV000639233 pathogenic Dilated cardiomyopathy 1O 2017-07-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1154 of the ABCC9 protein (p.Arg1154Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with Cantu syndrome (PMID: 22608503, 22610116) and in individuals with clinical features overlapping Cantu syndrome (PMID: 26656175, 26871653, 25790160). ClinVar contains an entry for this variant (Variation ID: 31946). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg1154Gln) has been determined to be pathogenic (PMID: 22608503, 23307537, 22610116). This suggests that the arginine residue is critical for ABCC9 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000024624 SCV000050490 pathogenic Hypertrichotic osteochondrodysplasia 2012-06-08 no assertion criteria provided literature only
Scripps Translational Science Institute,Scripps Health and The Scripps Research Institute RCV000024624 SCV000538206 pathogenic Hypertrichotic osteochondrodysplasia 2015-12-15 criteria provided, single submitter research

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