ClinVar Miner

Submissions for variant NM_012431.3(SEMA3E):c.1991C>T (p.Thr664Met) (rs375536813)

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
CeGaT Praxis fuer Humangenetik Tuebingen RCV000998823 SCV001155110 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Invitae RCV001053945 SCV001218232 uncertain significance CHARGE association 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 664 of the SEMA3E protein (p.Thr664Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs375536813, ExAC 0.01%). This variant has not been reported in the literature in individuals with SEMA3E-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000998823 SCV001551413 uncertain significance not provided no assertion criteria provided clinical testing The SEMA3E p.Thr604Met variant was not identified in the literature nor was it identified in the ClinVar, Cosmic or MutDB databases. The variant was identified in dbSNP (ID: rs375536813) and LOVD 3.0. The variant was identified in control databases in 1 of 249208 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 1 of 112562 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Thr604 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, and MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.