ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.430G>A (p.Glu144Lys) (rs121964966)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169074 SCV000220242 likely pathogenic Homocystinuria due to CBS deficiency 2014-04-14 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723427 SCV000331006 pathogenic not provided 2015-11-18 criteria provided, single submitter clinical testing
Invitae RCV000169074 SCV000649837 likely pathogenic Homocystinuria due to CBS deficiency 2017-04-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 144 of the CBS protein (p.Glu144Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121964966, ExAC 0.006%). This variant has been reported to co-occur in cis with the p.Arg439Gln variant in three individuals affected with homocystinuria (PMID: 9156316, 12124992). This variant has also been reported to co-occur in combination or in trans with other pathogenic variants in individuals with homocystinuria (PMID: 12124992, 7611293, 10215408). ClinVar contains an entry for this variant (Variation ID: 122). Experimental studies have shown that this variant severely impairs CBS enzyme activity in bacterial and yeast but not in higher eukaryotic cell systems (PMID: 22267502, 20506325, 25331909). In summary, this variant is a rare missense change which has been reported in affected individuals.  Additional functional or genetic data are needed to fully substantiate the pathogenicity of this variant. Therefore, it has been classified as Likely Pathogenic.
OMIM RCV000000144 SCV000020287 pathogenic Homocystinuria, pyridoxine-responsive 1995-07-01 no assertion criteria provided literature only

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.