ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.642+5G>A

dbSNP: rs755486893
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000809006 SCV000949140 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-11-21 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs755486893, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 653262). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with inconclusive levels of altered splicing (Invitae). 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.
Ambry Genetics RCV002363086 SCV002658586 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-14 criteria provided, single submitter clinical testing The c.642+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 6 in the SDHB gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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