Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001346717 | SCV001540941 | uncertain significance | Vici syndrome | 2018-02-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 2422 of the EPG5 protein (p.His2422Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EPG5-related disease. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV004619656 | SCV005118871 | uncertain significance | Inborn genetic diseases | 2024-04-08 | criteria provided, single submitter | clinical testing | The c.7266C>G (p.H2422Q) alteration is located in exon 42 (coding exon 42) of the EPG5 gene. This alteration results from a C to G substitution at nucleotide position 7266, causing the histidine (H) at amino acid position 2422 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |