Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186707 | SCV000240273 | uncertain significance | not provided | 2015-04-15 | criteria provided, single submitter | clinical testing | p.Asn126Ser (AAT>AGT): c.377 A>G in exon 3 of the ADSL gene (NM_000026.2) The Asn126Ser missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asn126Ser in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is conservative, as both Asparagine and Serine are uncharged, polar amino acid residues and it alters a position that is not highly conserved in the protein. However, multiple in-silico algorithms predict Asn126Ser is damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether Asn126Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV001035904 | SCV001199244 | uncertain significance | Adenylosuccinate lyase deficiency | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 126 of the ADSL protein (p.Asn126Ser). This variant is present in population databases (rs771267221, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 204811). 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 ADSL protein function. 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. |