Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000210583 | SCV000262863 | uncertain significance | Inborn genetic diseases | 2013-07-18 | criteria provided, single submitter | clinical testing | ​The c.4169A>G (p.Y1390C) alteration is located in exon 23 (coding exon N) of the EPG5 gene. This alteration results from a A to G substitution at nucleotide position 4169. The tyrosine (Y) at codon 1390 is replaced by cysteine (C).The missense change is rare in healthy cohorts:Based on data from the NHLBI Exome Sequencing Project (ESP), the EPG5 c.4169A>G (p.Y1390C) alteration was not observed among 6,039 individuals tested (0.0%). Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP).The altered amino acid is not conserved throughout evolution:The Y1390 amino acid is poorly conserved throughout vertebrates.The alteration is predicted benign by in silico models:TheY1390Calteration is predicted to be benign by Polyphen and tolerated by SIFT in silico analyses.Based on the available evidence, the deleterious nature of the EPG5 c.4169A>G (p.Y1390C) alteration is uncertain. |
| Invitae | RCV001060641 | SCV001225345 | uncertain significance | Vici syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 1390 of the EPG5 protein (p.Tyr1390Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs551488784, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 225001). 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"). 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. |