ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1594G>C (p.Ala532Pro)

gnomAD frequency: 0.00036  dbSNP: rs143764931
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767126 SCV000236007 likely benign not provided 2020-09-18 criteria provided, single submitter clinical testing Reported in association with HCM (Lopes et al., 2015); however, no specific clinical details were provided; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance by other clinical laboratories (ClinVar Variant ID# 201852; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 25351510)
Invitae RCV001079637 SCV000261974 likely benign Myofibrillar myopathy 4 2021-11-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000183539 SCV000271909 likely benign not specified 2020-01-08 criteria provided, single submitter clinical testing The p.Ala532Pro variant in LDB3 is classified as likely benign because it has been identified in 0.07% (85/128298) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org; dbSNP rs143764931). In addition, alanine (Ala) at position 532 is not conserved in evolution and proline (Pro) is present at this position in >10 bird and reptile species. ACMG/AMP Criteria applied: BS1.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769289 SCV000900667 likely benign Cardiomyopathy 2021-03-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000767126 SCV002049643 uncertain significance not provided 2021-04-14 criteria provided, single submitter clinical testing The LDB3 c.1594G>C; p.Ala532Pro variant (rs143764931) is reported in the literature in a cohort of individuals affected with hypertrophic cardiomyopathy, though it was not demonstrated to cause disease (Lopes 2015). This variant is found in the non-Finnish European population with an overall allele frequency of 0.07% (85/128298 alleles) in the Genome Aggregation Database. The alanine at codon 532 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.244). Given the lack of clinical and functional data, the significance of the p.Ala532Pro variant is uncertain at this time. References: Lopes LR et al. Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 Feb;101(4):294-301. PMID: 25351510.

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