ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1134G>C (p.Ala378=)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001387664 SCV001588336 pathogenic Hereditary hemorrhagic telangiectasia 2020-09-13 criteria provided, single submitter clinical testing This sequence change affects codon 378 of the ENG mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ENG protein. This variant also falls at the last nucleotide of exon 8 of the ENG coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 20414677, 15517393, 21158752; Invitae). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. For these reasons, this variant has been classified as Pathogenic.

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