ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.799G>A (p.Val267Met)

dbSNP: rs1057521126
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430573 SCV000521150 likely pathogenic not provided 2020-05-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with severely impaired mutant enzyme activity (Lenglet et al., 2018); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9199558, 9238757, 17298216, 17298218, 27769855, 29360981)
Invitae RCV000430573 SCV004294973 pathogenic not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 267 of the HMBS protein (p.Val267Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with acute intermittent porphyria (PMID: 9199558, 9238757; Invitae). ClinVar contains an entry for this variant (Variation ID: 381651). 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 HMBS protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects HMBS function (PMID: 29360981). For these reasons, this variant has been classified as Pathogenic.

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.