Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002337636 | SCV002637310 | uncertain significance | Cardiovascular phenotype | 2021-02-11 | criteria provided, single submitter | clinical testing | The p.V395F variant (also known as c.1183G>T), located in coding exon 10 of the EFEMP2 gene, results from a G to T substitution at nucleotide position 1183. The valine at codon 395 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well 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. |
| Labcorp Genetics |
RCV005096647 | SCV005793821 | uncertain significance | Cutis laxa, autosomal recessive, type 1B | 2024-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 395 of the EFEMP2 protein (p.Val395Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EFEMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1742839). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt EFEMP2 protein function with a negative predictive value of 95%. 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. |