ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.1221del (p.Trp408fs) (rs1361324844)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588547 SCV000695301 likely pathogenic Homocystinuria 2017-06-02 criteria provided, single submitter clinical testing Variant summary: The CBS c.1221delC (p.Trp408Glyfs) variant results in a premature termination codon, predicted to cause a truncated or absent CBS protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent from the large control database ExAC (0/120678 control chromosomes). One published report identified a compound heterozygous patient with a family history of homocystinuria who carried the variant along with a known pathogenic mutation (I278T; Gaustadnes_HM_2002). To our knowledge, functional studies on the variant have not been performed to date. Taken together, this variant is classified as likely pathogenic.
Counsyl RCV000666270 SCV000790532 likely pathogenic Homocystinuria due to CBS deficiency 2017-03-28 criteria provided, single submitter clinical testing
Invitae RCV000666270 SCV000963202 pathogenic Homocystinuria due to CBS deficiency 2019-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp408Glyfs*16) in the CBS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with homocystinuria due to CBS deficiency (PMID: 12124992). ClinVar contains an entry for this variant (Variation ID: 495530). Loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992). For these reasons, this variant has been classified as Pathogenic.

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