ClinVar Miner

Submissions for variant NM_000428.3(LTBP2):c.4934G>A (p.Arg1645Gln)

gnomAD frequency: 0.00004  dbSNP: rs371346534
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001975314 SCV002256077 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1645 of the LTBP2 protein (p.Arg1645Gln). This variant is present in population databases (rs371346534, gnomAD 0.2%). This missense change has been observed in individual(s) with primary congenital glaucoma (PMID: 27409795). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1463914). 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 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002074444 SCV002495829 uncertain significance Microspherophakia; Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3 2020-12-17 criteria provided, single submitter clinical testing LTBP2 NM_000428.2 exon 34 p.Arg1645Gln (c.4934G>A):This variant has been reported in the literature in the homozygous state in one proband with primary congenital glaucoma and segregated with disease in his affected brother (Michael 2016 PMID:27409795). This variant is also present in 0.01% (20/152208) of total alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-74502889-C-T?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV002484825 SCV002782997 uncertain significance Glaucoma 3, primary infantile, B; Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma 2021-11-15 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224599 SCV003920158 uncertain significance Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma 2021-03-30 criteria provided, single submitter clinical testing LTBP2 NM_000428.2 exon 34 p.Arg1645Gln (c.4934G>A):This variant has been reported in the literature in the homozygous state in one proband with primary congenital glaucoma and segregated with disease in his affected brother (Michael 2016 PMID:27409795). This variant is also present in 0.01% (20/152208) of total alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-74502889-C-T?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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