ClinVar Miner

Submissions for variant NM_022356.3(P3H1):c.940+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 RCV000686871 SCV000814410 likely pathogenic Osteogenesis imperfecta type 8 2018-04-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the P3H1 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 (rs762525651, ExAC 0.02%). This variant has not been reported in the literature in individuals with P3H1-related disease. 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 P3H1 are known to be pathogenic (PMID: 17277775, 19088120). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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