Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001345592 | SCV001539723 | uncertain significance | Cutis laxa, autosomal recessive, type 1B | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 310 of the EFEMP2 protein (p.Val310Met). This variant is present in population databases (rs544423133, gnomAD 0.03%). 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: 1041739). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EFEMP2 protein function with a negative predictive value of 80%. 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. |
Center for Genomics, |
RCV001345592 | SCV003919910 | uncertain significance | Cutis laxa, autosomal recessive, type 1B | 2022-08-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.02% [6/30608]; https://gnomad.broadinstitute.org/variant/11-65635812-C-T?dataset=gnomad_r2_1), and in ClinVar (Variation ID:1041739). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Ambry Genetics | RCV004995696 | SCV005572094 | uncertain significance | Cardiovascular phenotype | 2024-09-22 | criteria provided, single submitter | clinical testing | The p.V310M variant (also known as c.928G>A), located in coding exon 8 of the EFEMP2 gene, results from a G to A substitution at nucleotide position 928. The valine at codon 310 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |