ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.567C>T (p.Val189=) (rs35297577)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039085 SCV000062763 likely benign not specified 2012-03-19 criteria provided, single submitter clinical testing p.Val189Val in Exon 04 of JUP: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 0.2% (7/3734) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs35297577).
GeneDx RCV000039085 SCV000168905 benign not specified 2014-03-10 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.
Ambry Genetics RCV000251291 SCV000317826 likely benign Cardiovascular phenotype 2018-01-19 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001084270 SCV000560972 benign Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000463501 SCV001151300 likely benign not provided 2019-04-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000039085 SCV001362160 benign not specified 2019-06-03 criteria provided, single submitter clinical testing Variant summary: JUP c.567C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 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 0.0003 in 247354 control chromosomes, predominantly at a frequency of 0.0026 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 104 fold of the estimated maximal expected allele frequency for a pathogenic variant in JUP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.567C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (TTR c.424G>A, p.Val142Ile) at our laboratory providing supporting evidence for a benign role. 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/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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