ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1036G>A (p.Ala346Thr) (rs201968775)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150925 SCV000198561 likely benign not specified 2017-11-06 criteria provided, single submitter clinical testing p.Ala346Thr in exon 10 of LDB3: This variant is not expected to have clinical si gnificance due to frequency in the general population and a lack of conservation across species, including mammals. Of note, 4 non-human primates have a threoni ne (Thr) at this position. In addition, computational prediction tools do not su ggest a high likelihood of impact to the protein. It has also been identified in 0.13% (31/23778) of African chromosomes by the Genome Aggregation Database (gno mAD, http://gnomad.broadinstitute.org; dbSNP rs201968775). ACMG/AMP Criteria app lied: BS1, BP4 (Richards 2015).
GeneDx RCV000150925 SCV000235983 uncertain significance not specified 2015-06-08 criteria provided, single submitter clinical testing The A346T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. However, it has been seen in one other individual tested for DCM at GeneDx, and is reported in ClinVar as a variant of uncertain significance (Landrum et al., 2014). The A346T variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common, benign variant in these populations. Furthermore, this variant is a non-conservative amino acid substitution, which likely impacts secondary protein structure as these residues differ in polarity, charge, size and/or other properties, and this substitution occurs at a position that is conserved among mammals. Nonetheless, in silico analysis predicts this variant likely does not alter the protein structure/function. Moreover, missense mutations in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating this region of the protein may be tolerant of change.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Ambry Genetics RCV000619838 SCV000736758 uncertain significance Cardiovascular phenotype 2017-02-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000732675 SCV000860653 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing

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