ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.1849G>A (p.Asp617Asn) (rs757681761)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183231 SCV000235655 uncertain significance not provided 2017-05-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ABCC9 gene. The D617N variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D617N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis suggests that this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Invitae RCV000797250 SCV000936799 uncertain significance Dilated cardiomyopathy 1O 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 617 of the ABCC9 protein (p.Asp617Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs757681761, ExAC 0.003%). This variant has not been reported in the literature in individuals with ABCC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 201615). 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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