Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001778783 | SCV000250276 | uncertain significance | not provided | 2022-09-26 | criteria provided, single submitter | clinical testing | Identified in a patient with features of Marfan syndrome who was incidentally diagnosed with subclinical tuberous sclerosis complex when a maternally inherited TSC1 variant was identified through whole exome sequencing (Caylor et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (Callewaert et al., 2009; Frederic et al., 2009); Not located within exons 24-33, where the majority of pathogenic variants reported to date occur (Callewaert et al., 2009, Frederic et al., 2009); This variant is associated with the following publications: (PMID: 29926239, 19006240, 18767143) |
Illumina Laboratory Services, |
RCV000405761 | SCV000452626 | likely benign | Congenital contractural arachnodactyly | 2018-01-12 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Invitae | RCV000405761 | SCV000553213 | likely benign | Congenital contractural arachnodactyly | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002315590 | SCV000738421 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-05-20 | criteria provided, single submitter | clinical testing | The p.E846K variant (also known as c.2536G>A), located in coding exon 19 of the FBN2 gene, results from a G to A substitution at nucleotide position 2536. The glutamic acid at codon 846 is replaced by lysine, an amino acid with similar properties. This alteration was reported in a patient with suspicion of Marfan syndrome, but this variant was not thought to be responsible for the clinical phenotype (Caylor RC et al. Neurogenetics, 2018 Aug;19(3):205-213). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Center for Genomics, |
RCV001281014 | SCV001468418 | uncertain significance | Congenital contractural arachnodactyly; Macular degeneration, early-onset | 2021-03-30 | criteria provided, single submitter | clinical testing | FBN2 NM_001999.3 exon 19 p.Glu846Lys (c.2536G>A): This variant has not been reported in the literature but is present in 0.02% (37/129150) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-127697434-C-T). This variant is present in ClinVar (Variation ID:213392). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Revvity Omics, |
RCV001778783 | SCV003834037 | uncertain significance | not provided | 2020-05-29 | criteria provided, single submitter | clinical testing |