ClinVar Miner

Submissions for variant NM_003001.3(SDHC):c.1A>G (p.Met1Val) (rs755235380)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492170 SCV000581217 pathogenic Hereditary cancer-predisposing syndrome 2017-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Center for Human Genetics, Inc RCV000467345 SCV000782281 pathogenic Paragangliomas 3 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000791400 SCV000546039 pathogenic Gastrointestinal stroma tumor; Paragangliomas 3 2018-07-23 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the SDHC mRNA. An alternate in-frame methionine downstream of the initiator codon is located at codon 38. It is not known if this variant results in an absent or disrupted protein product. This variant is present in population databases (rs755235380, ExAC 0.02%). This variant has been reported in the literature in 3 individuals affected with paraganglioma/pheochromocytoma and gastrointestinal stromal tumors (PMID: 19454582, 22517554, 23282968), and has also been reported in a family with Paraganglioma Syndrome (PMID: 16249420). Two different variants (c.2T>A and c.3G>A) that disrupt the same methionine initiator have been reported in patients and families affected with head and neck paragangliomas (PMID: 19351833), paragangliomas (PMID: 11062460), and renal cell carcinoma (PMID: 22351710), indicating that this methionine initiator of SDHC may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.

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