ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.145G>C (p.Val49Leu)

dbSNP: rs200645175
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001071537 SCV001236845 uncertain significance Myofibrillar myopathy 4 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 49 of the LDB3 protein (p.Val49Leu). This variant is present in population databases (rs200645175, gnomAD 0.004%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 864365). 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.
Fulgent Genetics, Fulgent Genetics RCV002480445 SCV002786275 uncertain significance Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 2021-08-25 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003142032 SCV003816517 uncertain significance not provided 2019-02-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV003380845 SCV004098339 uncertain significance Cardiovascular phenotype 2023-07-24 criteria provided, single submitter clinical testing The p.V49L variant (also known as c.145G>C), located in coding exon 2 of the LDB3 gene, results from a G to C substitution at nucleotide position 145. The valine at codon 49 is replaced by leucine, an amino acid with highly similar properties. This variant has been detected in an individual from a dilated cardiomyopathy cohort (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003898078 SCV004708714 uncertain significance LDB3-related disorder 2023-10-28 criteria provided, single submitter clinical testing The LDB3 c.145G>C variant is predicted to result in the amino acid substitution p.Val49Leu. This variant was reported in an individual with dilated cardiomyopathy (Table S3, Mazzarotto et al. 2020. PubMed ID: 31983221). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-88439175-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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