ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.1341C>T (p.Phe447=) (rs34785693)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000241552 SCV000318179 likely benign Cardiovascular phenotype 2015-05-07 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768740 SCV000900110 benign Cardiomyopathy 2016-09-26 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000612145 SCV000734000 likely benign Dilated cardiomyopathy 1AA no assertion criteria provided clinical testing
GeneDx RCV000036871 SCV000166851 benign not specified 2013-10-03 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 RCV000036871 SCV000918389 benign not specified 2018-12-26 criteria provided, single submitter clinical testing Variant summary: ACTN2 c.1341C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0025 in 277002 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 100-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in ACTN2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000456350 SCV000563592 benign Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy 2017-12-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036871 SCV000060526 benign not specified 2012-03-22 criteria provided, single submitter clinical testing Phe447Phe in exon 12 of ACTN2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and has been identifie d in 0.4% (28/7020) of European American chromosomes from a broad, though clinic ally unspecified population (NHLBI Exome Sequencing Project; http://evs.gs.washi ngton.edu/EVS; dbSNP rs34785693).

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