ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)

dbSNP: rs104894230
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Total submissions: 33
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000207503 SCV000207845 pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect caused by increased phosphorylation of ERK, suggesting an activation of the RAS/MAPK pathway (Denayer et al., 2008; Niihori et al., 2011); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17979197, 28027064, 17601930, 30055033, 24224811, 21686750, 22317973, 21850009, 23093928, 16170316, 19035362, 24803665, 27589201, 24169525, 16835863, 30762279, 30885829, 31394527, 31560489, 33482860, 33224014)
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000207503 SCV000263054 pathogenic not provided 2014-06-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000013437 SCV000698555 pathogenic Costello syndrome 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The HRAS c.35G>C (p.Gly12Ala) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional studies showed that this variant increased RAS pathway activation in NIH 3T3 cells (Niihori_JHG_2011) and increased proliferation in Ba/F3 cells (Denayer_HM_2008). The variant of interest has not been found in a large, broad control population, ExAC in 120014 control chromosomes. This variant was reported in multiple Costello syndrome patients, including de novo occurrences (Aoki_NatGen_2005, Robbins_AJMG_2016, Niihori_JHG_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Ambry Genetics RCV000623953 SCV000741342 pathogenic Inborn genetic diseases 2016-03-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762848 SCV000893208 pathogenic Large congenital melanocytic nevus; Linear nevus sebaceous syndrome; Malignant tumor of urinary bladder; Costello syndrome; Epidermal nevus; Thyroid cancer, nonmedullary, 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000013437 SCV000956118 pathogenic Costello syndrome 2021-07-13 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813186 SCV002060961 pathogenic Noonan syndrome and Noonan-related syndrome 2021-04-06 criteria provided, single submitter clinical testing
OMIM RCV000013437 SCV000033684 pathogenic Costello syndrome 2005-10-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423741 SCV000506520 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433587 SCV000506521 likely pathogenic Prostate adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445257 SCV000506522 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426130 SCV000506523 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436832 SCV000506524 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444092 SCV000506525 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425989 SCV000506526 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435805 SCV000506527 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418547 SCV000506528 likely pathogenic Adenoid cystic carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428375 SCV000506529 likely pathogenic Nasopharyngeal neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435619 SCV000506530 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417508 SCV000506531 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428172 SCV000506532 likely pathogenic Thyroid tumor 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441501 SCV000506533 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423622 SCV000506534 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430806 SCV000506535 likely pathogenic Papillary renal cell carcinoma, sporadic 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440663 SCV000506536 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423413 SCV000506537 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433266 SCV000506538 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442448 SCV000506539 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422263 SCV000506540 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432956 SCV000506541 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445090 SCV000506542 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425511 SCV000506543 likely pathogenic Uterine carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001257536 SCV001434362 pathogenic Rhabdomyosarcoma 2020-09-01 no assertion criteria provided provider interpretation

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