ClinVar Miner

Submissions for variant NM_016955.4(SEPSECS):c.1178C>T (p.Ser393Leu)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV002510687 SCV002820200 uncertain significance Pontocerebellar hypoplasia type 2D criteria provided, single submitter clinical testing The missense variant c.1178C>T (p.Ser393Leu) in SEPSECS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser393Leu variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Ser at position 393 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Ser393Leu in SEPSECS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance .
Labcorp Genetics (formerly Invitae), Labcorp RCV002574741 SCV002940896 uncertain significance not provided 2022-10-13 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 393 of the SEPSECS protein (p.Ser393Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SEPSECS-related conditions (PMID: 31130284). 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 expected to disrupt SEPSECS 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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV002510687 SCV004801166 uncertain significance Pontocerebellar hypoplasia type 2D 2024-03-14 criteria provided, single submitter research

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.