Submissions for variant NM_000428.3(LTBP2):c.1295C>T (p.Pro432Leu)

gnomAD frequency: 0.00032  dbSNP: rs137854861

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000971799	SCV001119467	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Mendelics	RCV000989244	SCV001139486	uncertain significance	Weill-Marchesani syndrome 3	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001117709	SCV001275927	uncertain significance	Glaucoma 3, primary congenital, D	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001117710	SCV001275928	benign	Weill-Marchesani syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000971799	SCV001837362	benign	not provided	2020-02-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31589614, 27884173, 23401661)
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224148	SCV003920167	likely benign	Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma	2022-04-26	criteria provided, single submitter	clinical testing	This variant has been reported in the heterozygous state in one individual with primary open angle glaucoma and one with pseudoexfoliation syndrome (Jelodari-Mamaghani 2013 PMID:23401661). However, this variant is present in 0.8% (245/30610) of South Asian alleles in the Genome Aggregation Database, and in 1 homozygote in each of v2.1.1 and v3.1.2 (https://gnomad.broadinstitute.org/variant/14-75018994-G-A?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000971799	SCV004136901	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	LTBP2: BP4, BS2
Elahi Laboratory, University of Tehran	RCV000114805	SCV000148700	probable-pathogenic	Pseudoexfoliation glaucoma		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Reproductive Health Research and Development, BGI Genomics	RCV000114805	SCV001142442	uncertain significance	Pseudoexfoliation glaucoma	2020-01-06	no assertion criteria provided	curation	NM_000428.2:c.1295C>T in the LTBP2 gene has an allele frequency of 0.008 in South Asian subpopulation in the gnomAD database. The c.1295C>T (p.Pro432Leu) variant has been observed in a patient affected with pseudoexfoliation glaucoma (PEXG) syndrome (PMID: 23401661). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP4.