ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.274G>T (p.Asp92Tyr) (rs80338845)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791429 SCV000287820 pathogenic Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-09-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 92 of the SDHD protein (p.Asp92Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is known to be a common cause of disease, accounting for ~70% of all Dutch patients affected with paraganglioma and pheochromocytoma (PMID: 19584903, 21348866). Experimental studies in yeast have shown that this missense change causes reduction of SDH enzymatic activity (PMID: 26008905). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000567104 SCV000664566 pathogenic Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Good segregation with disease (lod 1.5-3 = 5-9 meioses),Strong segregation with disease (lod >3 = >10 meioses)
OMIM RCV000007305 SCV000027502 pathogenic Paragangliomas 1 2012-03-01 no assertion criteria provided literature only
OMIM RCV000007306 SCV000027503 pathogenic Pheochromocytoma 2012-03-01 no assertion criteria provided literature only
GeneReviews RCV000020520 SCV000040977 pathologic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2012-08-30 no assertion criteria provided curation Converted during submission to Pathogenic.

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