Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158985 | SCV000208924 | pathogenic | not provided | 2015-06-02 | criteria provided, single submitter | clinical testing | This mutation is denoted as c.34 G>C at the cDNA level or p.Gly12Arg (G12R) at the protein level. The G12R missense mutation in the NRAS gene has not been published as a germline mutation or benign polymorphism, to our knowledge. G12R has been reported previously as a somatic mutation in association with several different types of cancer (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010), primarily in haematopoietic and lymphoid tissues. A different missense substitution at the same position (G12C) has been seen at GeneDx several times and another (G12V) also has been reported previously as a somatic mutation (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010). In Filippi et al., a patient with the adjacent G13D mutation was described as having dysmorphic features (including macrocephaly, bilateral epicanthal folds and cafe-au-lait spots) in addition to clinical and heamological features consistent with a diagnosis of juvenile myelomonocytic leukemia (JMML) (Filippi et al., 2009). The variant is found in NOONAN panel(s). |
Equipe Genetique des Anomalies du Developpement, |
RCV001526619 | SCV001737049 | pathogenic | Increased nuchal translucency | criteria provided, single submitter | clinical testing | ||
3billion | RCV001781335 | SCV002318830 | pathogenic | Noonan syndrome 6 | 2022-03-22 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000040469). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID:28594414). Different missense change at the same codon have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000039648,VCV000040468,VCV000040470,VCV000177778, PMID:30417923,28594414,32888943,28594414,23334668). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.713>=0.6, 3CNET: 0.998>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV001781335 | SCV002512401 | pathogenic | Noonan syndrome 6 | 2021-11-27 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 supporting, PM1 moderate, PM2 moderate, PM6 strong, PP3 supporting |
Equipe Genetique des Anomalies du Developpement, |
RCV001781335 | SCV003843224 | pathogenic | Noonan syndrome 6 | 2021-02-08 | criteria provided, single submitter | clinical testing | |
Genesolutions, |
RCV001781335 | SCV003934964 | pathogenic | Noonan syndrome 6 | 2022-06-22 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000444217 | SCV000503736 | pathogenic | Melanoma | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425150 | SCV000503737 | pathogenic | Non-small cell lung carcinoma | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435447 | SCV000503738 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420396 | SCV000503739 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430635 | SCV000503740 | likely pathogenic | Chronic myelogenous leukemia, BCR-ABL1 positive | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438291 | SCV000503741 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420637 | SCV000503742 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430032 | SCV000503743 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440262 | SCV000503744 | likely pathogenic | Myelodysplastic syndrome | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423088 | SCV000503745 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only |