Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002785431 | SCV003025116 | uncertain significance | Spastic paraplegia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with arginine at codon 656 of the ZFYVE26 protein (p.Ser656Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs781719443, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with ZFYVE26-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Gene |
RCV004812458 | SCV005437761 | uncertain significance | not provided | 2024-06-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV004966093 | SCV005540092 | uncertain significance | Inborn genetic diseases | 2024-10-04 | criteria provided, single submitter | clinical testing | The c.1968T>A (p.S656R) alteration is located in exon 11 (coding exon 10) of the ZFYVE26 gene. This alteration results from a T to A substitution at nucleotide position 1968, causing the serine (S) at amino acid position 656 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |