ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.1223+1G>T

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806222 SCV000946209 pathogenic Homocystinuria due to CBS deficiency 2018-10-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 of the CBS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). While this particular variant has been not observed in the literature, a different variant (c.1223G>A, also known as IVS11+1G>A) at the same nucleotide of the consensus donor splice site was found in combination with a second rare CBS variant in an individual affected with homocystinuria (PMID: 12124992). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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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