Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003514300 | SCV004298031 | pathogenic | Huntington disease-like 1 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 183 of the PRNP protein (p.Thr183Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with dementia (PMID: 9266722, 10631141, 15558291). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13407). 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 PRNP protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects PRNP function (PMID: 10079068, 23527023, 26713717, 33731477). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000014347 | SCV000034596 | pathogenic | Spongiform encephalopathy with neuropsychiatric features | 1997-08-01 | no assertion criteria provided | literature only |