ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1130C>G (p.Pro377Arg) (rs113613074)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764479 SCV000895550 uncertain significance Familial cancer of breast; Megalencephaly cutis marmorata telangiectatica congenita; Lung cancer; Congenital macrodactylia; Keratosis, seborrheic; Epidermal nevus; Neoplasm of ovary; Capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth; Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi; Carcinoma of colon; Neoplasm of stomach; Cowden syndrome 5; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000461259 SCV000541312 uncertain significance Cowden syndrome 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 377 of the PIK3CA protein (p.Pro377Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs113613074, ExAC 0.01%). This variant has not been reported in the literature in individuals with PIK3CA-related disease. ClinVar contains an entry for this variant (Variation ID: 403909). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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.

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