ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.2200G>A (p.Val734Ile) (rs61688134)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000589913 SCV000884940 benign not provided 2017-09-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000251925 SCV000317866 benign Cardiovascular phenotype 2015-09-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Subpopulation frequency in support of benign classification,General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172738 SCV000051513 benign Myocardial infarction 2013-06-24 criteria provided, single submitter research
GeneDx RCV000038600 SCV000166793 benign not specified 2014-03-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000029274 SCV000051920 likely benign Cardiomyopathy 2015-10-20 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589913 SCV000698648 likely benign not provided 2016-08-02 criteria provided, single submitter clinical testing Variant summary: The ABCC9 c.2200G>A (p.Val734Ile) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 854/123698 control chromosomes (4 homozygotes) at a frequency of 0.0069039, which is approximately 276 times the estimated maximal expected allele frequency of a pathogenic ABCC9 variant (0.000025), suggesting this variant is benign polymorphism. This variant has been reported in patients with myocardial infarction, DCM, HCM, early repolarization syndrome, at least three of whom also carry a reported pathogenic variant, further supporting that this variant may be neutral (Hu_2013, Celestino-Soper_2015, Bottillo_2016). In addition, multiple clinical diagnostic laboratories classified this variant as benign. On the other hand, multiple studies showed p.Val734Ile may affect the function of ABCC9 (Smith_2013, Hu_2013). In a case-control study that included 584 Precocious Myocardial Infarction (PMI) patients and 873 controls, the frequency of 734Ile carriers was significantly higher in MI patients as compared to controls (crude OR=5.52, 95% CI=1.5319.84, P=0.0075, Minoretti_2006)). However, more samples may be needed to confirm whether this variant is associated with Precocious Myocardial Infarction. Taken together, this variant is classified as likely benign.
Invitae RCV000205535 SCV000262065 benign Dilated cardiomyopathy 1O 2018-01-06 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038600 SCV000062278 benign not specified 2012-02-17 criteria provided, single submitter clinical testing Val734Ile in exon 17 of ABCC9: This variant is not expected to be clinically sig nificant because it has been identified in 1.2% (87/7012) of European American c hromosomes chromosomes from a broad population by the NHLBI Exome Sequencing Pro ject (http://evs.gs.washington.edu/EVS; dbSNP rs61688134). Minoretti and colleag ues (2006) reported a possible association with an increased risk for myocardial infarction (based on an increased frequency in cases compared to controls), tho ugh this variant is unlikely to be disease causing when present in isolation.
PreventionGenetics RCV000038600 SCV000313468 benign not specified criteria provided, single submitter clinical testing

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