ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.1280C>T (p.Pro427Leu) (rs863223434)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197292 SCV000249714 pathogenic not provided 2014-12-09 criteria provided, single submitter clinical testing p.Pro427Leu (CCG>CTG): c.1280 C>T in exon 14 of the CBS gene (NM_000071.2). The P427L mutation in the CBS gene has been reported in one individual with a diagnosis of homocystinuria, based on clinical and biochemical findings (Mendes et al., 2014a). This individual was compound heterozygous for the P427L mutation and the S500L mutation. Functional studies showed that P427L causes impaired CBS enzyme activation by its allosteric activator, S-adenosylmethionine (Mendes et al., 2014a; Mednes et al., 2014b). P427L results in a semi-conservative amino acid substitution at a position that is conserved across species. Mutations in nearby residues (P422L, T434N, I435T) have been reported in association with homocystinuria, further supporting the functional importance of this region of the protein. Furthermore, the P427L mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, P427L in the CBS gene is interpreted as a disease-causing mutation. This variant was found in TAADV2-1
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000584030 SCV000692243 uncertain significance not specified 2016-03-15 no assertion criteria provided clinical testing

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