Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000995649 | SCV001149943 | likely pathogenic | Dopa-responsive dystonia due to sepiapterin reductase deficiency | 2018-12-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001869390 | SCV002171677 | uncertain significance | Dystonic disorder | 2024-04-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 175 of the SPR protein (p.Ala175Asp). This variant is present in population databases (no rsID available, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of SPR-related conditions (PMID: 33098801, 33822819, 35872528). ClinVar contains an entry for this variant (Variation ID: 807499). 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 expected to disrupt SPR protein function with a positive 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. |