Submissions for variant NM_007078.3(LDB3):c.160G>A (p.Gly54Ser)

gnomAD frequency: 0.00003  dbSNP: rs201786090

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079441	SCV000111320	uncertain significance	not provided	2013-06-10	criteria provided, single submitter	clinical testing
Invitae	RCV000706758	SCV000835827	uncertain significance	Myofibrillar myopathy 4	2023-07-26	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. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 54 of the LDB3 protein (p.Gly54Ser). This variant is present in population databases (rs201786090, gnomAD 0.005%). This missense change has been observed in individual(s) with hypertrophic or dilated cardiomyopathy (PMID: 24730657, 31983221, 32880476). ClinVar contains an entry for this variant (Variation ID: 93526). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive.
Ambry Genetics	RCV002390232	SCV002703123	uncertain significance	Cardiovascular phenotype	2021-11-09	criteria provided, single submitter	clinical testing	The p.G54S variant (also known as c.160G>A), located in coding exon 2 of the LDB3 gene, results from a G to A substitution at nucleotide position 160. The glycine at codon 54 is replaced by serine, an amino acid with similar properties. This variant was reported in an individual with severe hypertrophic cardiomyopathy (HCM) and in two dilated cardiomyopathy (DCM) cases with limited details (Fratev F et al. J Chem Inf Model, 2014 May;54:1524-36; Mazzarotto F et al. Circulation, 2020 02;141:387-398; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). This amino acid position is highly conserved in available 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 alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000079441	SCV001739864	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079441	SCV001954905	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000079441	SCV001968029	uncertain significance	not provided		no assertion criteria provided	clinical testing