Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001304857 | SCV001494158 | uncertain significance | CHARGE association | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 631 of the SEMA3E protein (p.Arg631Lys). This variant is present in population databases (rs553630404, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007643). 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 SEMA3E 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. |
Prevention |
RCV003908510 | SCV004726124 | uncertain significance | SEMA3E-related condition | 2024-02-06 | criteria provided, single submitter | clinical testing | The SEMA3E c.1892G>A variant is predicted to result in the amino acid substitution p.Arg631Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.11% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |