Submissions for variant NM_007078.3(LDB3):c.54G>T (p.Gln18His)

gnomAD frequency: 0.00001  dbSNP: rs149348427

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183544	SCV000236013	uncertain significance	not provided	2022-06-10	criteria provided, single submitter	clinical testing	Reported in a patient with sudden arrhythmogenic death syndrome (SADS) in the published literature, however this individual harbored additional cardiogenetic variants (Hata et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27005929)
Fulgent Genetics, Fulgent Genetics	RCV000763672	SCV000894552	uncertain significance	Dilated cardiomyopathy 1C; Myofibrillar myopathy 4	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817342	SCV000957896	uncertain significance	Myofibrillar myopathy 4	2024-12-26	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 18 of the LDB3 protein (p.Gln18His). This variant is present in population databases (rs149348427, gnomAD 0.008%). This missense change has been observed in individual(s) with sudden unexplained death or unexplained cardiac arrest (PMID: 27005929, 35352813). ClinVar contains an entry for this variant (Variation ID: 201856). 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. 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845500	SCV000987602	uncertain significance	Primary familial dilated cardiomyopathy		criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798640	SCV002043383	uncertain significance	Cardiomyopathy	2021-04-20	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000183544	SCV003816500	uncertain significance	not provided	2022-08-11	criteria provided, single submitter	clinical testing