Submissions for variant NM_020964.3(EPG5):c.7735C>T (p.Arg2579Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003016966	SCV003318185	uncertain significance	Vici syndrome	2022-08-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2579*) in the EPG5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the EPG5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. This variant disrupts a region of the EPG5 protein in which other variant(s) (p.Arg2579Gln) have been observed in individuals with EPG5-related conditions (PMID: 31625567). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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	RCV003016967	SCV003635306	uncertain significance	Inborn genetic diseases	2022-07-29	criteria provided, single submitter	clinical testing	Not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.