ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.290A>G (p.Gln97Arg) (rs762580653)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000201919 SCV000256644 uncertain significance Familial 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, ZASP-related 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 97 of the LDB3 protein (p.Gln97Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs762580653, ExAC 0.006%) but has not been reported in the literature in individuals with a LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 217828). 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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