ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*4050C>T (rs753530396)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236356 SCV000294127 uncertain significance not provided 2016-04-08 criteria provided, single submitter clinical testing A second variant of uncertain significance has also been identified in the PRX gene. The S1282L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1282L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000694151 SCV000822582 uncertain significance Charcot-Marie-Tooth disease type 4 2019-11-19 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 1282 of the PRX protein (p.Ser1282Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs753530396, ExAC 0.003%). This variant has not been reported in the literature in individuals with PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 246537). 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. 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.

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