ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.34G>T (p.Gly12Cys) (rs104894229)

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Total submissions: 34
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Miraca Genetics Laboratories, RCV000149829 SCV000196673 pathogenic Rasopathy no assertion criteria provided clinical testing Variant classified using ACMG guidelines
Blueprint Genetics RCV000212495 SCV000927854 pathogenic not provided 2018-08-14 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000440052 SCV000505663 likely pathogenic Bladder carcinoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439243 SCV000506496 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422023 SCV000506497 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431815 SCV000506498 likely pathogenic Nasopharyngeal Neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444512 SCV000506499 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424380 SCV000506500 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431602 SCV000506501 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443678 SCV000506502 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427213 SCV000506503 likely pathogenic Papillary renal cell carcinoma, sporadic 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437868 SCV000506504 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443826 SCV000506505 likely pathogenic Adenoid cystic carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426992 SCV000506506 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436802 SCV000506507 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419553 SCV000506508 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429404 SCV000506509 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436505 SCV000506510 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418395 SCV000506511 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429096 SCV000506512 likely pathogenic Neoplasm of the thyroid gland 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438902 SCV000506513 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421701 SCV000506514 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428012 SCV000506515 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438707 SCV000506516 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424087 SCV000506517 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434677 SCV000506518 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445233 SCV000506519 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Fulgent Genetics,Fulgent Genetics RCV000762849 SCV000893209 pathogenic Congenital giant melanocytic nevus; Epidermal nevus syndrome; Bladder cancer, somatic; Costello syndrome; Epidermal nevus; Follicular thyroid carcinoma 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000212495 SCV000207843 pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing The G12C pathogenic variant in the HRAS gene has been reported previously to be associated with Costello syndrome, including one de novo observation (Kerr et al., 2006, Niihori et al., 2011; Lorenz et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G12C is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Moreover, the glycine codons 12 and 13 of RAS proteins within the RAS/MAPK pathway are functionally important for GDP/GTP binding and are considered hot spots" for pathogenic variants (Wey et al. 2013; Gripp et al. 2012). Missense variants at the same (G12S/V/A/D) in nearby residues (G13C/D) have been reported in the Human Gene Mutation Database in association with Costello syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, functional studies of the G12C variant have shown that it results in increased active, GTP-bound HRAS (Niihori et al., 2011)."
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000013447 SCV000062132 pathogenic Costello syndrome 2012-11-20 criteria provided, single submitter clinical testing The Gly12Cys variant in HRAS has been reported in the literature in six individu als with severe neonatal Costello syndrome (Kerr 2006, Lo 2008, Lin 2009, Niihor i 2011, Lorenz 2012). This variant has been reported to have occurred de novo in one proband (Lorenz 2012). Several other DNA variants affecting codon 12 of HRA S are commonly observed in patients with Costello syndrome (Niihori 2011). There fore, this variant is highly likely to be pathogenic.
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000013447 SCV000263053 pathogenic Costello syndrome 2014-06-04 criteria provided, single submitter clinical testing
OMIM RCV000013447 SCV000033694 pathogenic Costello syndrome 2012-06-10 no assertion criteria provided literature only
OMIM RCV000029211 SCV000051857 pathogenic Nevus sebaceous 2012-06-10 no assertion criteria provided literature only
OMIM RCV000032851 SCV000056620 pathogenic Epidermal nevus 2012-06-10 no assertion criteria provided literature only

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