Submissions for variant NM_000428.3(LTBP2):c.3611C>T (p.Ala1204Val)

gnomAD frequency: 0.00057  dbSNP: rs45468895

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000967770	SCV001115188	benign	not provided	2025-01-31	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001027830	SCV001190450	uncertain significance	Microspherophakia; Glaucoma 3, primary congenital, D; Weill-Marchesani syndrome 3	2019-09-13	criteria provided, single submitter	clinical testing	LTBP2 NM_000428.2 exon 24 p.Ala1204Val (c.3611C>T): This variant has not been reported in the literature and is present in 0.8% (88/10332) of Ashkenazi Jewish alleles in the Genome Aggregation Database, including one homozygote (http://gnomad.broadinstitute.org/variant/14-74975348-G-A). 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	RCV001115836	SCV001273847	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.
Illumina Laboratory Services, Illumina	RCV001117267	SCV001275440	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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224499	SCV003920161	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 24 p.Ala1204Val (c.3611C>T): This variant has not been reported in the literature and is present in 0.8% (88/10332) of Ashkenazi Jewish alleles in the Genome Aggregation Database, including one homozygote (http://gnomad.broadinstitute.org/variant/14-74975348-G-A). 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.
GeneDx	RCV000967770	SCV005401370	uncertain significance	not provided	2024-05-18	criteria provided, single submitter	clinical testing	Has been reported as heterozygous in a patient with primary congenital glaucoma; however this variant was inherited from an unaffected parent (PMID: 27293371); Has also been observed in a patient with arrhythmogenic cardiomyopathy who had a causative variant in the DSG2 gene (PMID: 33917638); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33917638, 27293371)