Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002609044 | SCV002968008 | uncertain significance | not provided | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 77 of the SEMA3A protein (p.Ile77Val). This variant is present in population databases (rs746952334, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SEMA3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1923690). 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 SEMA3A 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. |
Ambry Genetics | RCV002634639 | SCV003729499 | uncertain significance | Inborn genetic diseases | 2022-10-04 | criteria provided, single submitter | clinical testing | The c.229A>G (p.I77V) alteration is located in exon 2 (coding exon 2) of the SEMA3A gene. This alteration results from a A to G substitution at nucleotide position 229, causing the isoleucine (I) at amino acid position 77 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004749928 | SCV005366832 | uncertain significance | SEMA3A-related disorder | 2024-04-30 | no assertion criteria provided | clinical testing | The SEMA3A c.229A>G variant is predicted to result in the amino acid substitution p.Ile77Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0085% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |