ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.689+10G>A (rs45563234)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038765 SCV000062443 benign not specified 2017-08-23 criteria provided, single submitter clinical testing c.689+10G>A in intron 04 of LDB3: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 0.3% (67/24532) of South Asian chromosomes, including 1 h omozygote, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstit ute.org; dbSNP rs45563234).
Invitae RCV000231371 SCV000289628 likely benign Myofibrillar myopathy, ZASP-related 2020-11-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000038765 SCV000340029 likely benign not specified 2016-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038765 SCV001426824 benign not specified 2020-07-27 criteria provided, single submitter clinical testing Variant summary: LDB3 c.689+10G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 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 0.0013 in 254596 control chromosomes, predominantly at a frequency of 0.0028 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 112 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 a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign (1x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as benign.
Athena Diagnostics Inc RCV000038765 SCV001476530 benign not specified 2020-03-19 criteria provided, single submitter clinical testing

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