ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.794G>A (p.Arg265His) (rs45458895)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183529 SCV000235996 uncertain significance not provided 2014-04-02 criteria provided, single submitter clinical testing p.Arg265His (CGC>CAC): c.794 G>A in exon 5 of the LDB3 gene (NM_007078.2). The R265H variant in the LDB3 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism to our knowledge. Although R265H results in a conservative amino acid substitution of one positively charged residue for another, the substitution occurs at a residue that is conserved across species. A mutation affecting a nearby residue (R268C) has been reported in association with myofibrillar myopathy. The R265H variant has been reported in dbSNP in 1/366 control chromosomes, however it 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.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in DCM,CARDIOMYOPATHY panel(s).
Ambry Genetics RCV000622255 SCV000735402 uncertain significance Cardiovascular phenotype 2020-01-15 criteria provided, single submitter clinical testing The p.R265H variant (also known as c.794G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 794. The arginine at codon 265 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, histidine is the reference amino acid in other 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 variant remains unclear.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769279 SCV000900657 uncertain significance Cardiomyopathy 2016-03-16 criteria provided, single submitter clinical testing
Invitae RCV000183529 SCV001004605 likely benign not provided 2019-01-02 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000183529 SCV001502622 uncertain significance not provided 2020-07-01 criteria provided, single submitter clinical testing
Loeys Lab,Universiteit Antwerpen RCV001375640 SCV001572565 uncertain significance Primary dilated cardiomyopathy 2021-02-26 criteria provided, single submitter clinical testing This sequence change results in a missense variant in the LDB3 gene (p.(Arg333His)). This variant is present in population databases with a prevalence of 36/282804 in GnomAD (BS1) . This variant has not been reported in the literature and no functional data are available. Prediction programs show conflicting results (Align GVGD: C0; Polyphen-2-HumDiv: possibly damaging ; Polyphen-2-HumVar: benign; SIFT: tolerated; MutationTaster: disease causing). The variant affects a highly conserved nucleotide and a moderately conserved amino acid. We identified this variant in a patients with DCM. In conclusion this variant was classified as a variant of unknown significance according to ACMG-guidelines (insufficient data, criteria for other classification are not met: BS1).
Invitae RCV001434419 SCV001637225 likely benign Myofibrillar myopathy, ZASP-related 2020-09-17 criteria provided, single submitter clinical testing

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