Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203761 | SCV001374937 | uncertain significance | Congenital contractural arachnodactyly | 2021-07-07 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FBN2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces tyrosine with cysteine at codon 2894 of the FBN2 protein (p.Tyr2894Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
| Ambry Genetics | RCV002375132 | SCV002684108 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-20 | criteria provided, single submitter | clinical testing | The p.Y2894C variant (also known as c.8681A>G), located in coding exon 65 of the FBN2 gene, results from an A to G substitution at nucleotide position 8681. The tyrosine at codon 2894 is replaced by cysteine, an amino acid with highly dissimilar properties. 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. |
| Gene |
RCV003227933 | SCV003924928 | uncertain significance | not provided | 2022-11-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |