ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.683_684del (p.Glu228fs)

dbSNP: rs762812025
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798175 SCV000937776 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu228Glyfs*27) in the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the SDHB protein. This variant is present in population databases (rs762812025, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with malignant paraganglioma (PMID: 16912137, 24694336). ClinVar contains an entry for this variant (Variation ID: 438428). This variant disrupts a region of the SDHB protein in which other variant(s) (p.Ser239Tyrfs*8) have been determined to be pathogenic (PMID: 15328326; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001025703 SCV001187946 pathogenic Hereditary cancer-predisposing syndrome 2019-03-09 criteria provided, single submitter clinical testing The c.683_684delAG pathogenic mutation, located in coding exon 7 of the SDHB gene, results from a deletion of two nucleotides at nucleotide positions 683 to 684, causing a translational frameshift with a predicted alternate stop codon (p.E228Gfs*27). This alteration has been seen in multiple patients with paragangliomas (Brouwers FM et al. J. Clin. Endocrinol. Metab. 2006 Nov;91:4505-9; Timmers HJ et al. J. Clin. Endocrinol. Metab. 2007 Mar;92:779-86; Welander J et al. J. Clin. Endocrinol. Metab. 2014 Jul;99:E1352-60; Sue M et al. Eur. J. Endocrinol. 2015 Feb;172:89-95; Jochmanova I et al. J. Cancer Res. Clin. Oncol. 2017 Aug;143:1421-1435). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Section on Medical Neuroendocrinolgy, National Institutes of Health RCV000505318 SCV000599527 pathogenic Hereditary pheochromocytoma-paraganglioma no assertion criteria provided research

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