ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.118A>C (p.Ile40Leu) (rs146276662)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202919 SCV000257881 uncertain significance Paragangliomas 1 2015-03-25 criteria provided, single submitter clinical testing
Invitae RCV000230632 SCV000287813 uncertain significance Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 40 of the SDHD protein (p.Ile40Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with Cowden or Cowden-like syndrome (PMID: 22829200). ClinVar contains an entry for this variant (Variation ID: 218581). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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 RCV000575031 SCV000675109 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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