Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697750 | SCV000826378 | uncertain significance | Pigmentary pallidal degeneration | 2018-06-19 | criteria provided, single submitter | clinical testing | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with Hallervoden-Spatz syndrome  in combination with another rare heterozygous variant in the same gene  (PMID: 12811783). This variant is also known as Tyr251Cys in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 361 of the PANK2 protein (p.Tyr361Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. |