ClinVar Miner

Submissions for variant NM_005163.2(AKT1):c.49G>A (p.Glu17Lys) (rs121434592)

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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000795313 SCV000934768 uncertain significance Cowden syndrome 6 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 17 of the AKT1 protein (p.Glu17Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121434592, ExAC 0.002%). This variant has not been reported in the literature in the germline of individuals with AKT1-related conditions. However, this variant has been reported as a somatic variant in approximately 3% of primary breast cancers (PMID: 23237847, 17611497, 20101210, 23000897) and reported as a de novo mosaic variant in 90% of individuals with Proteus syndrome (PMID: 21793738). Experimental studies have shown this variant leads to increased AKT1 activation and confers constitutive membrane localization of AKT1 in breast cancer cell lines (PMID: 23237847). 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.
OMIM RCV000015017 SCV000035273 pathogenic Breast adenocarcinoma 2011-08-18 no assertion criteria provided literature only
OMIM RCV000015018 SCV000035274 pathogenic Carcinoma of colon 2011-08-18 no assertion criteria provided literature only
OMIM RCV000015019 SCV000035275 pathogenic Neoplasm of ovary 2011-08-18 no assertion criteria provided literature only
OMIM RCV000031926 SCV000043964 pathogenic Proteus syndrome 2011-08-18 no assertion criteria provided literature only
GeneReviews RCV000031926 SCV000054577 pathologic Proteus syndrome 2012-08-09 no assertion criteria provided curation Converted during submission to Pathogenic.
Database of Curated Mutations (DoCM) RCV000431237 SCV000504510 likely pathogenic Endometrial Endometrioid Adenocarcinoma, Variant with Squamous Differentiation 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436698 SCV000504511 pathogenic Non-small cell lung cancer 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419412 SCV000504512 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430173 SCV000504513 pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440828 SCV000504514 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421850 SCV000504515 likely pathogenic Small cell lung cancer 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429060 SCV000504516 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439982 SCV000504517 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421009 SCV000504518 likely pathogenic Neoplasm of the thyroid gland 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431723 SCV000504519 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445271 SCV000504520 likely pathogenic Prostate neoplasm 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421696 SCV000504521 likely pathogenic Osteosarcoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434120 SCV000504522 likely pathogenic Meningeal Neoplasms 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444311 SCV000504523 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427484 SCV000504524 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438154 SCV000504525 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443761 SCV000504526 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426386 SCV000504527 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only

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