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

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169074	SCV000220242	likely pathogenic	Classic homocystinuria	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	Classic homocystinuria	2019-11-07	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, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000723427	SCV001246795	pathogenic	not provided	2018-08-01	criteria provided, single submitter	clinical testing
OMIM	RCV000000144	SCV000020287	pathogenic	Homocystinuria, pyridoxine-responsive	1995-07-01	no assertion criteria provided	literature only