Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001347098 | SCV001541343 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2020-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 2524 of the LRRK2 protein (p.Thr2524Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs748739318, ExAC 0.02%). This variant has been observed in individual(s) with early-onset Parkinson's disease, as well as unaffected individual(s) (PMID: 24565865). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |