ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.575C>T (p.Pro192Leu)

gnomAD frequency: 0.00001  dbSNP: rs758182278
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413437 SCV000492216 uncertain significance not specified 2016-11-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LDB3 gene. The P192L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P192L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, P192L is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Nevertheless, this substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001431796 SCV001634556 uncertain significance Myofibrillar myopathy 4 2023-06-23 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 373607). This variant is present in population databases (rs758182278, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 192 of the LDB3 protein (p.Pro192Leu). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.321+1532C>T in the primary transcript.
Ambry Genetics RCV002348134 SCV002650723 uncertain significance Cardiovascular phenotype 2023-12-22 criteria provided, single submitter clinical testing The p.P192L variant (also known as c.575C>T), located in coding exon 4 of the LDB3 gene, results from a C to T substitution at nucleotide position 575. The proline at codon 192 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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