Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000173950 | SCV000225138 | uncertain significance | not provided | 2015-04-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003502519 | SCV004292347 | uncertain significance | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 336 of the ACADM protein (p.Ser336Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MCAD deficiency (PMID: 22683754). ClinVar contains an entry for this variant (Variation ID: 193785). 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 ACADM protein function with a negative predictive value of 80%. This variant disrupts the p.Ser336 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been observed in individuals with ACADM-related conditions (PMID: 8198141, 22683754), which suggests that this may be a clinically significant amino acid residue. 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. |