Submissions for variant NM_001368067.1(LDB3):c.433G>A (p.Gly145Ser)

gnomAD frequency: 0.00009  dbSNP: rs376489385

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000618434	SCV000736688	uncertain significance	Cardiovascular phenotype	2016-10-20	criteria provided, single submitter	clinical testing	The p.G145S variant (also known as c.433G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 433. The glycine at codon 145 is replaced by serine, an amino acid with similar properties. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/12806) total alleles studied and 0.02% (2/8498) European American alleles. Based on data from ExAC, the A allele has an overall frequency of less than 0.01% (5/105598). 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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000661930	SCV000784255	uncertain significance	Myofibrillar myopathy 4	2018-03-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000661930	SCV000945451	uncertain significance	Myofibrillar myopathy 4	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 145 of the LDB3 protein (p.Gly145Ser). This variant is present in population databases (rs376489385, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy and dilated cardiomyopathy (PMID: 31737537, 36178741). ClinVar contains an entry for this variant (Variation ID: 518946). 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 tolerated. 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.
Klaassen Lab, Charite University Medicine Berlin	RCV000853126	SCV000995838	uncertain significance	Primary dilated cardiomyopathy	2019-07-03	criteria provided, single submitter	research
Mayo Clinic Laboratories, Mayo Clinic	RCV001509393	SCV001716077	uncertain significance	not provided	2021-12-23	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001509393	SCV001954029	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001509393	SCV001971163	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001509393	SCV002035165	uncertain significance	not provided		no assertion criteria provided	clinical testing