ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.147G>A (p.Val49=) (rs45591834)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038733 SCV000062411 benign not specified 2012-04-19 criteria provided, single submitter clinical testing Val49Val in Exon 02 of LDB3: 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 0.4% (27/7020) of Europe an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs45591834).
GeneDx RCV000038733 SCV000170107 benign not specified 2014-03-14 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.
PreventionGenetics,PreventionGenetics RCV000038733 SCV000306360 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000038733 SCV000335110 likely benign not specified 2015-09-17 criteria provided, single submitter clinical testing
Invitae RCV001079909 SCV000557553 benign Myofibrillar myopathy, ZASP-related 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620196 SCV000735358 likely benign Cardiovascular phenotype 2015-12-03 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770136 SCV000901562 benign Cardiomyopathy 2015-10-16 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845347 SCV000987395 likely benign not provided criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038733 SCV001519609 benign not specified 2021-03-11 criteria provided, single submitter clinical testing Variant summary: LDB3 c.147G>A alters a 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 0.003 in 251426 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 119 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDB3 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.147G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another likely pathogenic variant has been reported (TTN c.43732C>T, p.Gln14578Ter) in our internal database, providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.

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