ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.73-8A>G

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003213718 SCV003912636 likely pathogenic Hereditary cancer-predisposing syndrome 2024-04-03 criteria provided, single submitter clinical testing The c.73-8A>G intronic variant results from an A to G substitution 8 nucleotides upstream from coding exon 2 in the SDHB gene. This alteration has been observed in individuals with a personal and/or family history that is consistent with SDHB-related disease (Ambry internal data; Baptista P et al. Cureus 2022 Dec;14(12):e32504). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003779770 SCV004568392 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-04-01 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. RNA analysis provides insufficient evidence to determine the effect of this variant on SDHB splicing (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change falls in intron 1 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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