Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000157914 | SCV000207849 | pathogenic | not provided | 2017-03-22 | criteria provided, single submitter | clinical testing | The G13V missense change in the HRAS gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. Nevertheless, the vast majority of pathogenic HRAS germline mutations association with Costello syndrome alter the conserved glycine residues at positions 12 and 13, including the mutations G13D and G13C (Aoki et al., 2005; Estep et al., 2006; Gripp et al., 2006). Furthermore, 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. Additionally, G13V is not observed in large population cohorts (Lek et al., 2016). |
Integrated Genetics/Laboratory Corporation of America | RCV000590121 | SCV000698559 | likely pathogenic | Costello syndrome | 2019-03-11 | criteria provided, single submitter | clinical testing | Variant summary: HRAS c.38G>T (p.Gly13Val) results in a non-conservative amino acid change located in the Small GTP-binding protein domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 276492 control chromosomes (gnomAD). TThe variant of interest has been reported in numerous publications as a somatic mutation found in various types of cancers, but has not, to our knowledge, been reported as a germline mutation in Noonan or Costello Syndromes. However, Glycine 13 is one of the two most mutated amino acids in Costello Syndrome, and several other variants located at codon 13 have been associated with Costello Syndrome (G3C, G13D, G13S; Wey_2013). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Database of Curated Mutations |
RCV000442670 | SCV000504833 | likely pathogenic | Thymoma | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421468 | SCV000506560 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432148 | SCV000506561 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444507 | SCV000506562 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424767 | SCV000506563 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434580 | SCV000506564 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444587 | SCV000506565 | likely pathogenic | Uterine cervical neoplasms | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427265 | SCV000506566 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437080 | SCV000506567 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419846 | SCV000506568 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426169 | SCV000506569 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436822 | SCV000506570 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418712 | SCV000506571 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429433 | SCV000506572 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439230 | SCV000506573 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418565 | SCV000506574 | likely pathogenic | Chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428389 | SCV000506575 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Institute of Medical Sciences, |
RCV001255688 | SCV001432253 | pathogenic | Lip and oral cavity carcinoma | 2019-04-30 | no assertion criteria provided | research |