ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.57del (p.Leu20fs) (rs587776649)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482313 SCV000565548 pathogenic not provided 2016-05-23 criteria provided, single submitter clinical testing This deletion of one nucleotide in SDHD is denoted c.57delG at the cDNA level and p.Leu20CysfsX66 (L20CfsX66) at the protein level. The normal sequence, with the base that is deleted in braces, is CTCT[G]TTGC. The deletion causes a frameshift which changes a Leucine to a Cysteine at codon 20, and creates a premature stop codon at position 66 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. SDHD c.57delG has been reported at least once in an individual with a personal history of gastrointestinal stromal tumor (GIST), pheochromocytoma, and multiple paragangliomas (McWhinney 2007, Pasini 2008). Based on the currently available information, we consider this variant to be pathogenic.
Ambry Genetics RCV000492772 SCV000581225 pathogenic Hereditary cancer-predisposing syndrome 2015-10-03 criteria provided, single submitter clinical testing
Invitae RCV000641042 SCV000762660 pathogenic Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2017-10-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu20Cysfs*66) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587776649, ExAC 0.001%). This variant has been reported in an individual affected with gastrointestinal stromal tumor, pheochromocytoma, and multiple paragangliomas (PMID: 17667967). ClinVar contains an entry for this variant (Variation ID: 6917). Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007326 SCV000027524 pathogenic Paraganglioma and gastric stromal sarcoma 2008-01-01 no assertion criteria provided literature only
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505302 SCV000599532 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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