Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311200 | SCV000320513 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-12-01 | criteria provided, single submitter | clinical testing | The p.G475S variant (also known as c.1423G>A), located in coding exon 10 of the FBN2 gene, results from a G to A substitution at nucleotide position 1423. The glycine at codon 475 is replaced by serine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs200440156. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.86% (1/116) Mexican-American alleles. In population based cohorts in NHLBI Exome Sequencing Project (ESP), this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is 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 variant remains unclear. |
| Illumina Laboratory Services, |
RCV000322354 | SCV000452639 | uncertain significance | 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, 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 | RCV000322354 | SCV000553200 | benign | Congenital contractural arachnodactyly | 2023-09-10 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002487162 | SCV002781815 | uncertain significance | Congenital contractural arachnodactyly; Macular degeneration, early-onset | 2021-11-10 | criteria provided, single submitter | clinical testing |