Submissions for variant NM_000428.3(LTBP2):c.1978C>G (p.Arg660Gly)

dbSNP: rs199581688

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001027831	SCV001190451	uncertain significance	Microspherophakia; Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3	2019-04-15	criteria provided, single submitter	clinical testing	LTBP2 NM_000428.2 exon 10 p.Arg660Gly (c.1978C>G): This variant has not been reported in the literature and is present in 0.001% (2/113448) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-74999138-G-C). 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.
Illumina Laboratory Services, Illumina	RCV001117596	SCV001275801	uncertain significance	Weill-Marchesani syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001117597	SCV001275802	uncertain significance	Glaucoma 3, primary congenital, D	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001862418	SCV002268725	uncertain significance	not provided	2022-07-05	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with LTBP2-related conditions. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 828006). This variant is present in population databases (rs199581688, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 660 of the LTBP2 protein (p.Arg660Gly).
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224513	SCV003920163	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 10 p.Arg660Gly (c.1978C>G): This variant has not been reported in the literature and is present in 0.001% (2/113448) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-74999138-G-C). 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.