ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.2746C>T (p.Arg916Trp) (rs533032970)

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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 RCV000611084 SCV000731760 uncertain significance not specified 2017-06-28 criteria provided, single submitter clinical testing The p.Arg916Trp variant in ABCC9 has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis suggest that the p.Arg916Trp variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. In summary, the clinical significance of the p.Arg916Trp variant is unce rtain
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786078 SCV000924710 uncertain significance not provided 2017-10-16 no assertion criteria provided provider interpretation SCICD Classification: variant of uncertain significance based on limited data to associate this gene with disease and lack of case data. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Gene-level evidence: ABCC9: The ABCC9 gene encodes a cassette-binding protein that interacts with the Kir6.2 potassium channel. It is a gene of uncertain significance as its association with cardiomyopathy and atrial fibrillation is only emerging. ABCC9 is tolerant of both missense and loss of function variation, per a comparison or cases vs. patients with cardiomyopathy (Walsh et al 2016) and ExAC. Case data (not including our patient): ClinVar: not present. Cases in the literature: none reported. Segregation data: none reported. Functional data: none reported. In silico data (missense variants only): Per the test report, "Computational prediction tools and conservation analysis suggest that the p.Arg916Trp variant may impact the protein, though this information is not predictive enough to determine pathogenicity." Conservation data: The arginine at codon 916 is completely conserved across species. Neighboring amino acids are also conserved. Nearby pathogenic variants at this codon or neighboring codons: none. Population data: Highest MAF in South Asian population: 0.003%. The variant was reported online in 2 of 122,758 individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 1 of 15,385 individuals of South Asian descent (MAF=0.003%) and 1 of 55,592 individuals of European descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

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