ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1339C>G (p.Pro447Ala)

gnomAD frequency: 0.00005  dbSNP: rs397517211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038724 SCV000062402 uncertain significance not specified 2010-06-22 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000811808 SCV000952095 uncertain significance Myofibrillar myopathy 4 2023-12-07 criteria provided, single submitter clinical testing The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17060C>G in the primary transcript. This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 447 of the LDB3 protein (p.Pro447Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 45516) Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV002381312 SCV002690404 uncertain significance Cardiovascular phenotype 2022-09-15 criteria provided, single submitter clinical testing The p.P447A variant (also known as c.1339C>G), located in coding exon 9 of the LDB3 gene, results from a C to G substitution at nucleotide position 1339. The proline at codon 447 is replaced by alanine, an amino acid with highly similar properties. This alteration was reported in a case of sudden unexplained death and was seen with variants in other cardiac-related genes (Fadel S et al. Acad Forensic Pathol, 2020 Dec;10:166-175). This amino acid position is well conserved in available vertebrate species. 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.
Fulgent Genetics, Fulgent Genetics RCV002477105 SCV002785838 uncertain significance Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 2021-09-08 criteria provided, single submitter clinical testing

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