ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.3590G>A (p.Arg1197His) (rs755156050)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620662 SCV000736618 uncertain significance Cardiovascular phenotype 2016-07-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000428844 SCV000532557 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ABCC9 gene. The R1197H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1197H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, R1197H is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000548252 SCV000639236 uncertain significance Dilated cardiomyopathy 1O 2017-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1197 of the ABCC9 protein (p.Arg1197His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs755156050, ExAC 0.01%). This variant has not been reported in the literature in individuals with ABCC9-related disease. ClinVar contains an entry for this variant (Variation ID: 389883). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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