ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.1557C>A (p.Ile519=) (rs150120464)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000241646 SCV000318717 benign Cardiovascular phenotype 2015-10-23 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769110 SCV000900483 benign Cardiomyopathy 2016-10-11 criteria provided, single submitter clinical testing
GeneDx RCV000038799 SCV000169798 benign not specified 2013-03-11 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 RCV000038799 SCV000920336 benign not specified 2018-03-06 criteria provided, single submitter clinical testing Variant summary: VCL c.1557C>A 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 0.0022 in 277816 control chromosomes in the gnomAD database and literature, including 4 homozygotes. The observed variant frequency is approximately 87.11 fold of the estimated maximal expected allele frequency for a pathogenic variant in VCL causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. c.1557C>A has been reported in the literature in one individual affected with palpitations (Campuzano_2012). This report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000230596 SCV000289908 benign Dilated cardiomyopathy 1W 2017-12-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038799 SCV000062477 benign not specified 2012-04-17 criteria provided, single submitter clinical testing Ile519Ile in Exon 12 of VCL: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence and has been identified in 1.3% (49/3738) of Africa n American chromosomes from a broad population by the NHLBI Exome Sequencing Pro ject (http://evs.gs.washington.edu/EVS; dbSNP rs150120464).

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