Submissions for variant NM_020964.3(EPG5):c.6691G>A (p.Gly2231Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002701443	SCV003002475	uncertain significance	Vici syndrome	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2231 of the EPG5 protein (p.Gly2231Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1959753). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EPG5 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.
Ambry Genetics	RCV002701444	SCV003696245	uncertain significance	Inborn genetic diseases	2021-07-15	criteria provided, single submitter	clinical testing	The c.6691G>A (p.G2231R) alteration is located in exon 39 (coding exon 39) of the EPG5 gene. This alteration results from a G to A substitution at nucleotide position 6691, causing the glycine (G) at amino acid position 2231 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.