ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.904G>A (p.Glu302Lys) (rs779270933)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723460 SCV000700449 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing
Invitae RCV000594989 SCV000769924 pathogenic Homocystinuria due to CBS deficiency 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 302 of the CBS protein (p.Glu302Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs779270933, ExAC 0.01%). This variant has been reported in two siblings affected with homocystinuria in combination with another CBS variant (PMID: 10338090) and in unrelated affected individuals (PMID: 12124992, 29326875, Invitae). Experimental studies have shown that this missense change reduces CBS enzyme activity in vitro with protein missfolding and a higher proteolytic kinetics than wild-type (PMID: 10338090, 22267502, 20506325). For these reasons, this variant has been classified as Pathogenic.

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