ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.2031G>A (p.Pro677=) (rs188888662)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000126387 SCV000169891 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000126387 SCV000270296 likely benign not specified 2015-07-30 criteria provided, single submitter clinical testing p.Pro677Pro in Exon12 of JUP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 31/66738 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs188888662).
Ambry Genetics RCV000619251 SCV000736646 likely benign Cardiovascular phenotype 2016-06-29 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001085716 SCV000766959 likely benign Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000645217 SCV001151287 likely benign not provided 2018-12-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001127663 SCV001287000 uncertain significance Naxos disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001127664 SCV001287001 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 12 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170358 SCV001332932 likely benign Cardiomyopathy 2019-02-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000126387 SCV001362158 benign not specified 2019-01-21 criteria provided, single submitter clinical testing Variant summary: JUP c.2031G>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 0.00023 in 277244 control chromosomes (gnomAD). The observed variant frequency is approximately 23-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in JUP causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2031G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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