ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.797G>A (p.Arg266Lys) (rs121964969)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621987 SCV000738475 pathogenic Cardiovascular phenotype 2017-06-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual(s) satisfying established diagnostic criteria for classic disease in trans with a mutation or mutation is homozygous,Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes) ,Deficient protein function by in vitro/ex vivo assay
Counsyl RCV000469164 SCV000790684 likely pathogenic Homocystinuria due to CBS deficiency 2017-10-09 criteria provided, single submitter clinical testing
Invitae RCV000469164 SCV000543517 pathogenic Homocystinuria due to CBS deficiency 2016-10-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 266 of the CBS protein (p.Arg266Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (rs121964969, ExAC no frequency). This variant has been reported in the homozygous state in three individuals affected with pyridoxine-responsive CBS deficiency, and in the compound heterozygous state in several other affected individuals (PMID: 9361025). ClinVar contains an entry for this variant (Variation ID: 125). Experimental studies have shown that this missense change causes significantly reduced CBS activity and impairs the function of the protein (PMID: 9361025, 16619244, 22738154, 22267502, 22333527, 20506325, 22612060). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000147 SCV000020290 pathogenic Homocystinuria, pyridoxine-responsive 1997-12-01 no assertion criteria provided literature only

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