ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.3346C>T (p.Arg1116Cys) (rs387907228)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000809546 SCV000949699 pathogenic Dilated cardiomyopathy 1O 2019-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1116 of the ABCC9 protein (p.Arg1116Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with Cantu syndrome and observed to segregate with clinical features of Cantu syndrome in a family, and observed de novo in an individual with clinical features of Cantu syndrome (PMID: 22610116, 27316244, Invitae). ClinVar contains an entry for this variant (Variation ID: 35534). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg1116 amino acid residue in ABCC9. Other variant(s) that disrupt this residue have been observed in individuals with ABCC9-related conditions (PMID: 25590979, 23307537, 22610116), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV001249678 SCV001423631 likely pathogenic Kleefstra syndrome 1 2018-06-11 criteria provided, single submitter clinical testing [ACMG/AMP: PM2, PM5, PP2, PP3, PP5] This alteration is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].
OMIM RCV000029189 SCV000051834 pathogenic Hypertrichotic osteochondrodysplasia Cantu type 2012-05-18 no assertion criteria provided literature only

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