Submissions for variant NM_007078.3(LDB3):c.1422G>A (p.Ser474=)

gnomAD frequency: 0.00136  dbSNP: rs142625982

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038726	SCV000062404	likely benign	not specified	2015-02-18	criteria provided, single submitter	clinical testing	p.Ser474Ser in exon 12 of LDB3: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.1% (91/66282) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs142625982).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038726	SCV000698753	benign	not specified	2017-06-19	criteria provided, single submitter	clinical testing	Variant summary: The LDB3 c.1422G>A (p.Ser474Ser) variant involves the alteration of a non-conserved nucleotide causing a synonymous change that 4/5 splice prediction tools predict change of a cryptic splicing acceptor site. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 301/264076 control chromosomes (gnomAD) at a frequency of 0.0011398, which is approximately 46 times the estimated maximal expected allele frequency of a pathogenic LDB3 variant (0.000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Therefore, due to the nature and location of this variant, control population frequency, and additional clinical diagnostic laboratories classifying the variant as "likely benign/benign," the variant of interest has been classified as Benign.
Ambry Genetics	RCV000619945	SCV000736503	likely benign	Cardiovascular phenotype	2015-12-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV003502511	SCV001001046	benign	Myofibrillar myopathy 4	2024-01-28	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170177	SCV001332727	likely benign	Cardiomyopathy	2018-01-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000860874	SCV001829898	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000860874	SCV002821522	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	LDB3: BS1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000860874	SCV001744335	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038726	SCV001923311	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000860874	SCV001931518	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038726	SCV001953067	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000860874	SCV001975222	likely benign	not provided		no assertion criteria provided	clinical testing