Total submissions: 3
| 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. |