ClinVar Miner

Submissions for variant NM_002296.4(LBR):c.1757G>A (p.Arg586His)

gnomAD frequency: 0.00002  dbSNP: rs573510559
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002534249 SCV003523498 likely pathogenic not provided 2024-02-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 586 of the LBR protein (p.Arg586His). This variant is present in population databases (rs573510559, gnomAD 0.03%). This missense change has been observed in individual(s) with autosomal recessive LBR-related conditions (PMID: 23824842, 34567078, 36307859). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 545626). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LBR protein function with a positive predictive value of 80%. This variant disrupts the p.Arg586 amino acid residue in LBR. Other variant(s) that disrupt this residue have been observed in individuals with LBR-related conditions (PMID: 30448303), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province RCV003163026 SCV003915607 likely pathogenic Greenberg dysplasia 2022-08-28 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796263 SCV005418641 pathogenic Pelger-Huët anomaly; Greenberg dysplasia; Reynolds syndrome; Regressive spondylometaphyseal dysplasia criteria provided, single submitter clinical testing PM2_Supporting+PP3_Moderate+PM3_VeryStrong+PP4
OMIM RCV000656653 SCV000778792 pathogenic Regressive spondylometaphyseal dysplasia 2022-02-03 no assertion criteria provided literature only
New York Genome Center RCV001836859 SCV002097792 uncertain significance Pelger-Huët anomaly 2021-03-19 flagged submission clinical testing

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