Submissions for variant NM_001368067.1(LDB3):c.511G>A (p.Ala171Thr)

gnomAD frequency: 0.00015  dbSNP: rs373632943

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150920	SCV000198549	uncertain significance	not specified	2013-04-09	criteria provided, single submitter	clinical testing	The Ala171Thr variant in LDB3 has not been reported in the literature but has pr eviously been identified by our laboratory in 3 individuals of Ashkenazi Jewish ancestry (1 with HCM, 1 with DCM, and 1 with DCM and LVNC). This variant has be en identified in 2/8514 European American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/). It is possible that this varian t is common in the Ashkenazi Jewish population but appropriate control cohorts w oudl need to be sequenced to determine this. Computational analyses (biochemica l amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not pr ovide strong support for or against an impact to the protein. Additional studie s are needed to fully assess the clinical significance of this variant.
GeneDx	RCV001704086	SCV000490600	likely benign	not provided	2020-12-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24647531, 25351510)
Invitae	RCV000467142	SCV000557537	likely benign	Myofibrillar myopathy 4	2024-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621927	SCV000736985	uncertain significance	Cardiovascular phenotype	2016-04-08	criteria provided, single submitter	clinical testing	The p.A171T variant (also known as c.511G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 511. The alanine at codon 171 is replaced by threonine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs373632943. Based on data from ExAC, the A allele has an overall frequency of approximately 0.04% (44/105556). Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/12874) total alleles studied and 0.02% (2/8514) European American alleles. 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 variant remains unclear.
Illumina Laboratory Services, Illumina	RCV000467142	SCV001259681	uncertain significance	Myofibrillar myopathy 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Revvity Omics, Revvity	RCV001704086	SCV003816505	uncertain significance	not provided	2023-05-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975175	SCV004786471	likely benign	LDB3-related disorder	2023-05-04	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).