ClinVar Miner

Submissions for variant NM_181882.2(PRX):c.3186G>T (p.Lys1062Asn) (rs139188673)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000236373 SCV000614805 likely benign not specified 2016-11-04 criteria provided, single submitter clinical testing
GeneDx RCV000766571 SCV000293108 uncertain significance not provided 2018-12-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRX gene. The K1062N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 204/126628 (0.2%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The K1062N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000474498 SCV000551416 uncertain significance Charcot-Marie-Tooth disease type 4 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1062 of the PRX protein (p.Lys1062Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs139188673, ExAC 0.2%). This variant has not been reported in the literature in individuals with PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 245910). 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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