ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.955G>A (p.Ala319Thr)

gnomAD frequency: 0.00001  dbSNP: rs151219713
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183530 SCV000235997 uncertain significance not provided 2012-09-04 criteria provided, single submitter clinical testing p.Ala319Thr (GCT>ACT): c.955 G>A in exon 7 of the LDB3 gene (NM_007078.2). The Ala319Thr variant in the LDB3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ala319Thr results in a non-conservative amino acid substitution of non-polar Alanine residue with a polar Threonine residue at a position that is conserved until rat. However, no mutations have been reported in this region of the LDB3 gene, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Ala319Thr is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s).
Ambry Genetics RCV000618440 SCV000736485 uncertain significance Cardiovascular phenotype 2022-12-19 criteria provided, single submitter clinical testing The p.A319T variant (also known as c.955G>A), located in coding exon 7 of the LDB3 gene, results from a G to A substitution at nucleotide position 955. The alanine at codon 319 is replaced by threonine, an amino acid with similar properties. This variant has been detected in a sudden cardiac death case and in individuals reported to have dilated cardiomyopathy (DCM) or who were included in DCM cohorts; however, clinical details were limited and additional variants in cardiac-related genes were also detected (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398; Suktitipat B et al. PLoS One, 2017 Jul;12:e0180056; VanDyke RE et al. J Genet Couns, 2021 Apr;30:503-512). This amino acid position is highly 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.
Invitae RCV001246927 SCV001420319 uncertain significance Myofibrillar myopathy 4 2023-04-07 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 201844). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). This variant is present in population databases (rs151219713, gnomAD 0.05%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 319 of the LDB3 protein (p.Ala319Thr). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*7215G>A in the primary transcript.
Fulgent Genetics, Fulgent Genetics RCV002478627 SCV002788282 uncertain significance Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 2021-10-12 criteria provided, single submitter clinical testing

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