Total submissions: 33
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV000207503 | SCV000263054 | pathogenic | not provided | 2014-06-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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, |
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, |
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 |
RCV000423741 | SCV000506520 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433587 | SCV000506521 | likely pathogenic | Prostate adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000445257 | SCV000506522 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426130 | SCV000506523 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436832 | SCV000506524 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444092 | SCV000506525 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425989 | SCV000506526 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435805 | SCV000506527 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418547 | SCV000506528 | likely pathogenic | Adenoid cystic carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428375 | SCV000506529 | likely pathogenic | Nasopharyngeal neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435619 | SCV000506530 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000417508 | SCV000506531 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428172 | SCV000506532 | likely pathogenic | Thyroid tumor | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441501 | SCV000506533 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423622 | SCV000506534 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430806 | SCV000506535 | likely pathogenic | Papillary renal cell carcinoma, sporadic | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440663 | SCV000506536 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423413 | SCV000506537 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433266 | SCV000506538 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442448 | SCV000506539 | likely pathogenic | Myelodysplastic syndrome | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422263 | SCV000506540 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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 |
RCV000445090 | SCV000506542 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425511 | SCV000506543 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Human Genome Sequencing Center Clinical Lab, |
RCV001257536 | SCV001434362 | pathogenic | Rhabdomyosarcoma | 2020-09-01 | no assertion criteria provided | provider interpretation |