Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001932618 | SCV002170754 | uncertain significance | Vici syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with alanine at codon 2526 of the EPG5 protein (p.Ser2526Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs772963749, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV003167053 | SCV003877178 | uncertain significance | Inborn genetic diseases | 2023-01-24 | criteria provided, single submitter | clinical testing | The c.7576T>G (p.S2526A) alteration is located in exon 44 (coding exon 44) of the EPG5 gene. This alteration results from a T to G substitution at nucleotide position 7576, causing the serine (S) at amino acid position 2526 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |