ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.765+1G>A

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001384747 SCV001584388 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-07-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 7) of the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with with paraganglioma-pheochromocytoma syndromes (PMID: 15328326). This variant is also known as 899+1G/A in the literature. 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. This variant disrupts the C-terminus of the SDHB protein. Other variant(s) that disrupt this region (exon 8 deletion) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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