Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000201919 | SCV000256644 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2015-03-11 | criteria provided, single submitter | research | The LDB3 Gln97Arg is a rare variant and is present in the Exome Aggregation Consortium dataset (MAF=0.000008; http://exac.broadinstitute.org/). We identified this variant in a HCM proband of Indian descent. who also carries another variant (MYBPC3 Arg1022His) of "uncertain significance". The proband has no family history of disease or SCD. Computational tools SIFT and PolyPhen-2 predict this variant to be "tolerated" and "benign" respectively, however MutationTaster predicts the variant to be "disease-causing". In summary, based on the rarity in general populations and our limited familial data we have classify LDB3 Gln97Arg as a variant of "uncertain significance". Further evidence is required to fully understand its pathogenic role in HCM. |
Invitae | RCV000546674 | SCV000638666 | uncertain significance | Myofibrillar myopathy 4 | 2022-09-27 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 217828). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs762580653, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 97 of the LDB3 protein (p.Gln97Arg). |