ClinVar Miner

Submissions for variant NM_003923.3(FOXH1):c.122T>C (p.Met41Thr)

gnomAD frequency: 0.00002  dbSNP: rs369306218
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001881507 SCV002151554 uncertain significance Holoprosencephaly sequence 2021-03-26 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 41 of the FOXH1 protein (p.Met41Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. While this variant is present in population databases (rs369306218), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with FOXH1-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 disruptive, 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.

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.