ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.715G>A (p.Val239Ile)

gnomAD frequency: 0.00008  dbSNP: rs201417512
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171992 SCV000050976 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000171992 SCV000235994 likely benign not provided 2020-09-01 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23861362)
Invitae RCV001217126 SCV001388957 uncertain significance Myofibrillar myopathy 4 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 192 of the LDB3 protein (p.Val192Ile). This variant is present in population databases (rs201417512, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 191697). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002362880 SCV002662532 uncertain significance Cardiovascular phenotype 2023-12-29 criteria provided, single submitter clinical testing The p.V239I variant (also known as c.715G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 715. The valine at codon 239 is replaced by isoleucine, an amino acid with highly similar properties. This alteration (described as NM_001080116.1:c.574G>A p.V192I) has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This variant has also been reported in a sudden death case (described as NM_001171610 c.919G>A p.V307I) and a hypertrophic cardiomyopathy (HCM) case; however, both individuals had co-occurring variants and limited clinical details (Hertz CL et al. Int J Legal Med, 2016 Jan;130:91-102; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen RCV000171992 SCV001338887 not provided not provided no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 01-06-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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