Submissions for variant NM_007078.3(LDB3):c.1697T>G (p.Met566Arg)

gnomAD frequency: 0.00006  dbSNP: rs566463138

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221610	SCV000271911	uncertain significance	not specified	2015-05-07	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Met556Arg var iant in LDB3 has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.2% (14/8652) of East Asian chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs5664631 38). Computational prediction tools and conservation analysis suggest that the p .Met556Arg variant may impact the protein, though this information is not predic tive enough to determine pathogenicity. In summary, while the clinical significa nce of the p.Met556Arg variant is uncertain, its frequency in the general popula tion suggests that it is more likely to be benign.
Invitae	RCV001428629	SCV001631331	likely benign	Myofibrillar myopathy 4	2024-01-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399789	SCV002714052	likely benign	Cardiovascular phenotype	2019-09-05	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.
GeneDx	RCV003317158	SCV004021566	uncertain significance	not provided	2023-07-11	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Variant vetted as missense in alternate transcript NM_007078.2; This variant is associated with the following publications: (PMID: 32344918, 33949037, 35284542)
PreventionGenetics, part of Exact Sciences	RCV003967590	SCV004784450	likely benign	LDB3-related disorder	2020-10-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).