Submissions for variant NM_007078.3(LDB3):c.80T>C (p.Leu27Pro)

dbSNP: rs1057517864

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414048	SCV000490912	uncertain significance	not specified	2016-12-13	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the LDB3 gene. The L27P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This 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. Thee L27P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800067	SCV000939766	uncertain significance	Myofibrillar myopathy 4	2020-03-06	criteria provided, single submitter	clinical testing	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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 372570). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 27 of the LDB3 protein (p.Leu27Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline.
Ambry Genetics	RCV004022162	SCV005025088	uncertain significance	Cardiovascular phenotype	2022-11-27	criteria provided, single submitter	clinical testing	The p.L27P variant (also known as c.80T>C), located in coding exon 1 of the LDB3 gene, results from a T to C substitution at nucleotide position 80. The leucine at codon 27 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.