ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.405+1del

dbSNP: rs1558182956
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691372 SCV000819148 likely pathogenic Gastrointestinal stromal tumor; Paragangliomas 3 2019-11-08 criteria provided, single submitter clinical testing 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. A different variant affecting this nucleotide (c.405+1G>T) has been determined to be pathogenic (PMID: 17667967, 24402737, 24758179, 12658451). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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 has not been reported in the literature in individuals with SDHC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 5) of the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

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