ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.325C>T (p.Gln109Ter) (rs1060503770)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456537 SCV000554047 pathogenic Pheochromocytoma; Paragangliomas 1 2016-11-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the SDHD mRNA at codon 109 (p.Gln109*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 51 amino acids of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families affected with pheochromocytomas (PCC) or paragangliomas (PGL) (PMID: 11897817, 19454582, 25720320). While no functional studies have been performed to test the effects of this particular variant on SDHD protein function or stability, it deletes 51 C-terminal amino acid residues from the SDHD protein. A founder mutation (p.Leu139Pro) has been reported in this region (PMID: 21348866, 11391798), and a downstream truncating variant has been classified as likely pathogenic in the Invitae database, indicating that the C-terminal amino acid residues may be critical for SDHD function. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492697 SCV000581233 pathogenic Hereditary cancer-predisposing syndrome 2015-11-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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