Submissions for variant NM_005612.5(REST):c.1583A>G (p.His528Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV003154609	SCV003843164	uncertain significance	Wilms tumor 6	2022-11-22	criteria provided, single submitter	clinical testing	The REST c.1583A>G (p.His528Arg) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with a personal or family history of Wilms tumor. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005100930	SCV005822813	uncertain significance	not provided	2024-08-04	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 528 of the REST protein (p.His528Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with REST-related conditions. ClinVar contains an entry for this variant (Variation ID: 2444899). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.