ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr) (rs397514565)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806643 SCV000946653 pathogenic Cowden syndrome 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 378 of the PIK3CA protein (p.Cys378Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with megalencephaly-capillary malformation syndrome (MCAP) (PMID: 27631024). It has also been reported in the mosaic state in several individuals with symptoms consistent with PIK3CA-related overgrowth syndrome (PMID: 28151489, 27631024, 22729224). ClinVar contains an entry for this variant (Variation ID: 39704). 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 and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000032908 SCV000056680 pathogenic Megalencephaly cutis marmorata telangiectatica congenita 2012-06-24 no assertion criteria provided literature only
Genomics and Pathology Services,Washington University in St.Louis RCV000201233 SCV000255988 pathogenic PIK3CA related overgrowth spectrum 2014-12-08 no assertion criteria provided clinical testing

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