ClinVar Miner

Submissions for variant NM_003907.3(EIF2B5):c.944G>A (p.Arg315His)

gnomAD frequency: 0.00003  dbSNP: rs113994064
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070077 SCV001235287 pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 315 of the EIF2B5 protein (p.Arg315His). This variant is present in population databases (rs113994064, gnomAD 0.007%). This missense change has been observed in individuals with leukoencephalopathy with vanishing white matter (PMID: 11704758, 17646634; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5950). 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 EIF2B5 protein function with a negative predictive value of 80%. This variant disrupts the p.Arg315 amino acid residue in EIF2B5. Other variant(s) that disrupt this residue have been observed in individuals with EIF2B5-related conditions (PMID: 11704758, 15136673, 21307862), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001070077 SCV002765624 likely pathogenic not provided 2022-12-13 criteria provided, single submitter clinical testing Functional studies in lymphocytes from a patient who had the R315H variant as well as another EIF2B5 variant suggest reduction of guanine exchange activity compared to wild-type; however, additional studies are needed to validate the functional effect of this variant on its own (Horzinski et al., 2010); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21307862, 17646634, 26162493, 20016818, 15136673, 11704758, 33084218, 34745209, 20958979)
Fulgent Genetics, Fulgent Genetics RCV003221416 SCV002797192 likely pathogenic Leukoencephalopathy with vanishing white matter 5 2024-01-22 criteria provided, single submitter clinical testing
OMIM RCV003221416 SCV000026496 pathogenic Leukoencephalopathy with vanishing white matter 5 2007-07-24 no assertion criteria provided literature only
Natera, Inc. RCV000006314 SCV001460706 pathogenic Vanishing white matter disease 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.