ClinVar Miner

Submissions for variant NM_020297.4(ABCC9):c.4512+711G>A

gnomAD frequency: 0.00006  dbSNP: rs72559751
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001061813 SCV001226571 uncertain significance Dilated cardiomyopathy 1O 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1513 of the ABCC9 protein (p.Ala1513Thr). This variant is present in population databases (rs72559751, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or sudden cardiac death (PMID: 15034580, 34076677). ClinVar contains an entry for this variant (Variation ID: 856369). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCC9 protein function. Experimental studies have shown that this missense change affects ABCC9 function (PMID: 15034580). 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.
CeGaT Center for Human Genetics Tuebingen RCV001311294 SCV001501406 uncertain significance not provided 2020-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001311294 SCV001804782 uncertain significance not provided 2023-03-13 criteria provided, single submitter clinical testing Identified in an individual with a personal and family history of idiopathic dilated cardiomyopathy; the variant was not present in the unaffected parent but DNA was not available from the affected parent to confirm segregation with disease (Bienengraeber et al., 2004); Reported as an incidental finding in a fetus with multiple congenital anomalies; the variant was paternally inherited and the father was informed he should have a cardiology exam (Corsten-Janssen et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies show abnormal channel gating, suggesting that this variant affects ATP-dependent pore regulation (Bienengraeber et al., 2004); however, additional studies are needed to clarify the effect of this variant in vivo; Reported using an alternate transcript of the gene; This variant is associated with the following publications: (PMID: 15034580, 34076677, 32627857)
Fulgent Genetics, Fulgent Genetics RCV002479365 SCV002779415 uncertain significance Hypertrichotic osteochondrodysplasia Cantu type; Dilated cardiomyopathy 1O; Atrial fibrillation, familial, 12; Intellectual disability and myopathy syndrome 2021-11-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV003307898 SCV003993364 likely benign Cardiovascular phenotype 2023-04-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001311294 SCV001743412 likely pathogenic not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001311294 SCV001930368 likely pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001311294 SCV001973089 likely pathogenic not provided no assertion criteria provided clinical testing

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