Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000196818 | SCV000250130 | uncertain significance | not provided | 2017-02-14 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN2 gene. The M2469V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, the M2469V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Although the M2469V variant is located within a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with CCA (Collod-Beroud et al., 2003; Frederic et al., 2009). |
Invitae | RCV000537713 | SCV000630256 | likely benign | Congenital contractural arachnodactyly | 2023-08-01 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000196818 | SCV003800223 | uncertain significance | not provided | 2022-07-08 | criteria provided, single submitter | clinical testing | The FBN2 c.7405A>G; p.Met2469Val variant (rs863223546), to our knowledge, is not reported in the medical literature but reported in the ClinVar database (Variation ID: 213250). This variant is observed on two alleles in the Genome Aggregation Database. The methionine at codon 2469 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.247). Due to limited information, the clinical significance of this variant is uncertain at this time. |