Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001148892 | SCV001309813 | uncertain significance | Vanishing white matter disease | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Fulgent Genetics, |
RCV001148892 | SCV002777849 | uncertain significance | Vanishing white matter disease | 2022-04-20 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002559432 | SCV003463229 | uncertain significance | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with phenylalanine at codon 571 of the EIF2B5 protein (p.Cys571Phe). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is present in population databases (rs375421867, ExAC 0.05%). This variant has not been reported in the literature in individuals with EIF2B5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |