Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001247102 | SCV001420505 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2021-08-02 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 640 of the PRX protein (p.Lys640Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs781739632, ExAC 0.06%). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRX-related conditions. |
Ambry Genetics | RCV002411909 | SCV002723336 | uncertain significance | Inborn genetic diseases | 2020-11-24 | criteria provided, single submitter | clinical testing | The p.K640R variant (also known as c.1919A>G), located in coding exon 4 of the PRX gene, results from an A to G substitution at nucleotide position 1919. The lysine at codon 640 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |