ClinVar Miner

Submissions for variant NM_003907.3(EIF2B5):c.1340C>T (p.Ser447Leu)

dbSNP: rs113994080
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004169 SCV001162965 pathogenic Vanishing white matter disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001390107 SCV001591729 pathogenic not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 447 of the EIF2B5 protein (p.Ser447Leu). This variant is present in population databases (rs113994080, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of leukoencephalopathy with vanishing white matter (PMID: 14566705, 19158808, 19170749). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 813359). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001390107 SCV001985996 uncertain significance not provided 2021-08-02 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 19158808, 21307862, 19170749, 14566705, 16998732, 30315562, 25761052, 31438897)
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001004169 SCV002054021 pathogenic Vanishing white matter disease criteria provided, single submitter clinical testing
Natera, Inc. RCV001004169 SCV002079153 pathogenic Vanishing white matter disease 2020-04-23 no assertion criteria provided clinical testing

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