Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000476271 | SCV000553187 | likely benign | Congenital contractural arachnodactyly | 2025-01-30 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000476271 | SCV001318246 | 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. |
| Gene |
RCV001566251 | SCV001789742 | uncertain significance | not provided | 2024-10-16 | criteria provided, single submitter | clinical testing | Reported in two Dutch individuals with aortic aneurysm and/or dissection (PMID: 29907982); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19006240, 18767143, 29907982) |
| Ambry Genetics | RCV002429546 | SCV002744306 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-01-07 | criteria provided, single submitter | clinical testing | The p.R906H variant (also known as c.2717G>A), located in coding exon 21 of the FBN2 gene, results from a G to A substitution at nucleotide position 2717. The arginine at codon 906 is replaced by histidine, an amino acid with highly similar properties. This variant was reported in two individuals from a thoracic aortic aneurysm and dissection (TAAD) cohort; however, clinical details were limited (Overwater E et al. Hum Mutat, 2018 09;39:1173-1192). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782388 | SCV005394353 | likely benign | not specified | 2024-09-16 | criteria provided, single submitter | clinical testing | Variant summary: FBN2 c.2717G>A (p.Arg906His) results in a non-conservative amino acid change located in the TB domain (IPR017878) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251404 control chromosomes. The observed variant frequency is approximately 85.92 fold of the estimated maximal expected allele frequency for a pathogenic variant in FBN2 causing Aortopathy phenotype (1.3e-06). c.2717G>A has been reported in the literature in individuals affected with Aortopathy (Overwater_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Aortopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 29907982). ClinVar contains an entry for this variant (Variation ID: 411821). Based on the evidence outlined above, the variant was classified as likely benign. |