ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.737-1G>C (rs757428597)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000544919 SCV000797640 likely pathogenic Homocystinuria due to CBS deficiency 2018-02-02 criteria provided, single submitter clinical testing
Invitae RCV000544919 SCV000649847 pathogenic Homocystinuria due to CBS deficiency 2018-11-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 of the CBS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs757428597, ExAC 0.002%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with homocystinuria (PMID: 14635102). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 471366). 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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