Submissions for variant NM_007078.3(LDB3):c.147G>A (p.Val49=)

gnomAD frequency: 0.00312  dbSNP: rs45591834

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038733	SCV000062411	benign	not specified	2012-04-19	criteria provided, single submitter	clinical testing	Val49Val in Exon 02 of LDB3: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence and has been identified in 0.4% (27/7020) of Europe an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs45591834).
GeneDx	RCV000038733	SCV000170107	benign	not specified	2014-03-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000038733	SCV000335110	likely benign	not specified	2015-09-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079909	SCV000557553	benign	Myofibrillar myopathy 4	2025-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620196	SCV000735358	likely benign	Cardiovascular phenotype	2015-12-03	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770136	SCV000901562	benign	Cardiomyopathy	2015-10-16	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845347	SCV000987395	likely benign	not provided		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038733	SCV001519609	benign	not specified	2021-03-11	criteria provided, single submitter	clinical testing	Variant summary: LDB3 c.147G>A alters a conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.003 in 251426 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 119 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDB3 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.147G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another likely pathogenic variant has been reported (TTN c.43732C>T, p.Gln14578Ter) in our internal database, providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000845347	SCV003800122	benign	not provided	2023-09-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000845347	SCV004126998	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	LDB3: BP4, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000845347	SCV005221811	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003891484	SCV000306360	benign	LDB3-related disorder	2022-11-14	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000845347	SCV001744196	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038733	SCV001918767	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000845347	SCV001929789	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038733	SCV001955839	benign	not specified		no assertion criteria provided	clinical testing