ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.440A>G (p.Tyr147Cys) (rs774568101)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469133 SCV000554000 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 147 of the SDHB protein (p.Tyr147Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs774568101, ExAC 0.04%), including at least one homozygous individual. This variant has been reported in an individual affected with pheochromocytoma (PMID: 28229225). ClinVar contains an entry for this variant (Variation ID: 412466). Experimental studies have shown that this missense change results in altered SDHB subcellular localization, and significant reduction of SDH activity in vitro (PMID: 28229225). 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 RCV000492611 SCV000581187 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Mendelics RCV000708786 SCV000837735 uncertain significance Cowden syndrome 2018-07-02 criteria provided, single submitter clinical testing

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