Submissions for variant NM_000428.3(LTBP2):c.587A>G (p.Gln196Arg)

gnomAD frequency: 0.00032  dbSNP: rs374099324

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001117817	SCV001276043	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	RCV001117818	SCV001276044	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	RCV001856547	SCV002151390	uncertain significance	not provided	2023-04-12	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 196 of the LTBP2 protein (p.Gln196Arg). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 885925). This variant has not been reported in the literature in individuals affected with LTBP2-related conditions. This variant is present in population databases (rs374099324, gnomAD 0.1%).
Fulgent Genetics, Fulgent Genetics	RCV002505692	SCV002816888	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	2021-10-08	criteria provided, single submitter	clinical testing